INSECT CONTROL GENE DSF AND METHODS OF USE

Abstract: Present invention is based on the discovery and isolation of the dissatisfaction (DSF) gene and its protein product. An isolated polynucleotide encoding DSF, substantially pure DSF polypeptide, and an antibody that binds to DSF polypeptide are provided. Also provided are: a DNA construct that comprises a disrupted DSF gene which can prevent functional DSF expression, a transgenic insect having a transgene disrupting DSF expression, a method of producing transgenic insect comprising DSF gene, and a method of identifying a compound that affects the activity of a DSF polypeptide.

Description: INSECT CONTROL GENE DSF AND METHODS OF USE STATEMENT AS TO FEDERALLY SPONSORED RESEARCH This invention was made with Government support under Grant Nos. GM36549, CA14195, MH57460, T32CA09370 and F32NS09735 awarded by the National Institutes of Health. The Government has certain rights in this invention. FIELD OF THE INVENTION The present invention relates generally to reproductive behavior, and more specifically to the dissatisfaction (DSF) gene, its protein product and methods of use. BACKGROUND OF THE INVENTION Reproductive behavior in Drosophila can be divided into a series of stereotypical sex-specific activities, performed by males or females, which are released and modified by specific environmental clues (Hall, Science 264:1702-14. 1994). Male courtship begins with orientation toward the female and continues through tapping, following, "singing" a species specific song by vibrating an extended wing, licking, and copulation. Virgin female responses to male courtship include mild rejection of a courting male as well as receptive behaviors that facilitate copulation, while mated females respond to male courtship with a strong rejection response (Connolly et al, Behavior_$:86-l 11, 1973). Little is known about the genes involved with specific control of sexual behavior. The primary determinant of sex in Drosophila is the ratio of X chromosomes to autosomes (X:A ratio). Information about this ratio is passed through Sex-lethal (Sxl), transformer (tra), transformer-2 (tra2) and doublesex (dsx) to genes involved in differentiation (see e.g., McKeown, Curr. Opin. Genet. Dev. 2:299-303, 1992). The dissatisfaction (DSF) gene locus of Drosophila melanogaster was identified in a screen for mutations yielding abnormal sexual behavior (Finley et al, Proc. Natl. Acad. Sci. USA 94:913, 1997). This screen was based on the premise that some fraction of female-sterile mutations that lead to a failure to lay eggs will alter sexual behavior and neural development. As part of this screen a collection of existing egg-laying-defective female-sterile mutations (Schupbach et al, Genetics 129: 119-1136, 1991) was screened for alterations in female and male behavior. One mutation in this screen, identified by its isolation number, RC32, resulted in abnormal sexual behavior and neural development in both males and females. This locus was renamed dissatisfaction and the RC32 allele referred to as DSF1. As described in Finley et al, 1997, supra, DSF mutant males are bisexual, courting both males and females, and have significant difficulty in copulating as a result of poor performance of the abdominal bend necessary for copulation. This poor abdominal bending correlates with abnormal neuromuscular junctions on the ventral muscles of abdominal segment 5. DSF mutant females are resistant to male courtship, and also are resistant to males during copulation. Although normal eggs are produced and sperm stored normally, eggs are never laid. The failure to lay eggs correlates with an absence of motor neuronal synapses on the circular muscles of the uterus. Aside from the changes in neuromuscular junctions on the ventral abdominal muscles of males and the uterine muscles of females, all other neuromuscular junctions appear normal. SUMMARY OF THE INVENTION The present invention is based on the discovery and isolation of the dissatisfaction (DSF) gene and its protein product. In one embodiment, substantially pure dissatisfaction (DSF) polypeptide and functional fragments thereof are provided. Invention polypeptides are useful as immunogens for producing antibodies which bind to a DSF polypeptide or functional fragment thereof. In another embodiment, isolated polynucleotides encoding DSF polypeptide, functional fragments thereof and polynucleotides complementary thereto are provided. Further provided are polynucleotides containing an expression control element controlling expression of an operatively linked nucleic acid in a manner substantially similar to DSF polypeptide expression. Also provided are vectors containing invention polynucleotides, probes that selectively hybridize thereto and host cells transformed therewith. In yet another embodiment, transgenic insects having a transgene disrupting expression of DSF, chromosomally integrated into the cells of the insect are provided. Nucleic acid constructs including a disrupted DSF gene, such that the disruption prevents expression of functional DSF polypeptide, and host cells transformed therewith, also are provided. In still another embodiment, transgenic insects having a transgene encoding a DSF polypeptide or functional fragment thereof are provided. Methods for producing transgenic insects including, introducing into the genome of an insect to obtain a transformed insect, invention polynucleotides encoding DSF polypeptide or functional fragment thereof operatively linked to a promoter which functions in insect cells to cause the production of an RNA sequence, and obtaining a transgenic insect having a nucleic acid encoding DSF or functional fragment thereof also are provided. Methods for identifying compounds that modulate DSF activity or expression of a polynucleotide encoding DSF, including incubating components comprising a test compound, and a DSF polypeptide or functional fragment thereof, or a cell expressing a DSF polypeptide or functional fragment thereof, under conditions sufficient to allow the components to interact, and detecting an effect of the test compound on DSF polypeptide activity or expression of a polynucleotide encoding DSF also are provided. Such compounds, including agonists and antagonists of DSF activity or expression of a polynucleotide encoding DSF, can be useful for identifying DSF biological activities. Candidate test compounds include insect hormones, libraries thereof, and combinatorial libraries. Methods for isolating proteins that bind to DSF polypeptide or functional fragment thereof, including incubating at least one protein and a DSF polypeptide under conditions sufficient to allow binding, bound DSF polypeptide or functional fragment thereof from unbound, and isolating the protein that binds to the DSF polypeptide or functional fragment thereof are provided. Methods for identifying proteins that interact with a DSF polypeptide or functional fragment thereof in a cell, including obtaining a cell expressing DSF polypeptide or functional fragment thereof which also expresses a protein suspected of interacting with DSF polypeptide or functional fragment thereof, detecting an interaction between DSF polypeptide or functional fragment thereof with an interacting protein, isolating the interacting protein form the cell and identifying the protein that interacts with a DSF polypeptide or functional fragment thereof also are provided. Cell based methods for identifying interacting proteins can employ chimeras in which a suspected interacting protein encoded by a nucleic acid is linked to an activation domain. Interaction of a suspect protein with DSF or functional fragment thereof can thereby activate expression of an appropriate reporter gene. Methods for identifying a nucleic acid sequence that selectively binds to a DSF polypeptide or functional fragment thereof including contacting at least one nucleic acid sequence with a DSF polypeptide or functional fragment thereof under conditions allowing binding, detecting binding of a nucleic acid sequence to a DSF polypeptide or functional fragment thereof, isolating the bound nucleic acid sequence and identifying the sequence also are provided. Such methods are useful for identifying binding sequences from a random plurality of oligonucleotide sequences. Further provided are agricultural compositions comprising invention polypeptides, polynucleotides, antibodies, transgenic insects and compounds that modulate DSF activity or expression of a polynucleotide encoding DSF. Insecticidal compositions include transgenic insects having disrupted expression of DSF and compounds that modulate DSF activity or expression of a polynucleotide encoding DSF which are useful for effecting control of insect pests. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic diagram showing cosmid contigs in the region around DSF. Thick dark lines indicate the DNA deleted in various chromosomal deficiencies in salivary chromosome regions 25 and 26. Arrowheads indicate that the deletion extends farther than is shown. The dashed line in Df(2L)cl-h2 indicates that the right hand breakpoint has not been characterized molecularly, but is known from genetic analyses, to fall within Df(2L)50078a. Thin lines indicate cosmids containing genomic DNA from the region. Triangles at the top of the figure represent P-element insertions. P-element P[w + ] 13321 was obtained from the Berkeley Drosophila Genome Project. Mobilization of P[w + ]13321 was used to generate the 79 and 402 P-element insertions. Figure 2 is a schematic diagram of the subdivision of the DSF-containing region by additional deletions and transformational rescue. The thin line at the top of the figure is an Eco Rl restriction map of the DSF region (in kb) as found in the cosmids obtained from the European Drosophila Genome Project. Thick black bars indicate some of the cosmids obtained from the European Drosophila Genome Project. The thick grey bar represents a P-element cosmid which rescues the DSF mutant phenotype. Triangles represent the 79 and 402 P-element insertions. Open bars indicate deleted regions. Df(2L)dsf5 is the smallest dsf deletion. Other deletions extending left and right from the 402 P-element that are limited to the 30 kb EcoRI fragment do not eliminate DSF function. Figure 3 is a schematic diagram of a DSF gene. Sequence analysis of the region reveals a gene encoding a nuclear receptor-like protein. The first identified exon contains in-frame stop codons preceding an ATG codon in a good context for initiation. A cDNA in which this exon is spliced directly into an exon encoding the first finger is spliced directly to an exon encoding the second finger of the DNA binding domain. The sequence encoding a T/A box, a motif following directly after the DNA binding domain (Kurokawa et al, Genes and Dev. _:1423-1435, 1993), is encoded downstream and is joined directly to the second DNA binding domain exon by use of well defined splice junctions. The T/A box-encoding region also encodes a linker region and the first portion of the ligand binding domain (LBD). The ligand binding domain encoding region is followed by an in frame stop codon terminating the normal protein. The positions of the three EMS induced DSF alleles, dsfl, dsfό and dsfl, and the molecular changes of those mutations are indicated. Figure 4 is a nucleic acid sequence of DSF (SEQ ID NO: 1). Figure 5 is an amino acid sequence of DSF polypeptide (SEQ ID NO:2). Figure 6 shows the protein sequence of a DNA binding domain and a T/A region of DSF (SEQ ID NO:3). The sequence of DSF from the first amino acid to the end of the T/A box is shown. * indicates the cysteine residues that coordinate the two zinc atoms of the illustrated DNA binding motif. The P box and D box sequences are underlined and noted. The P box forms a DNA recognition helix that determines the preferred nucleotide half site sequences for binding (Umenso et al. , Cell 57:1139- 1146, 1989; Mader et al, Nature 338:271-274, 1989). The second glycine of the P box (bold) is changed to an aspartic acid residue (D) by the DSF6 mutation. The D box is involved in determining the spacing between the P box-binding DNA half sites favored by receptor dimers (Umesono et al, 1989, supra; Luisi et al, Nature 352:497-505, 1991; Rastinejad et al, Nature 375:203-211). The D box of DSF is nine amino acids, longer than other known D boxes and suggestive of unique spacing between the DNA sites recognized by homo or heterodimers. The T box and A box sequences are based on those defined in Kurokawa et al, supra, 1993, and are underlined and noted. Figure 7 shows the amino acid sequence of a DSF ligand binding domain (SEQ ID NO:4). The DSF sequence extends 9 amino acids beyond the sequence shown. The glutamine reside at position 50 (Q, underlined and bold) of the sequence shown is converted to STOP (Z) in the DSF1 mutation. Figure 8 shows a schematic comparison between DSF and human tailless and their percent identity. The DNA binding domains are located near the N-termini and the ligand binding domains are localized very near the C-termini. Figure 9 shows an alignment of the DNA binding and T/A regions of DSF protein (SEQ ID NO: 5) and human tailless protein (SEQ ID NO:6). Alignment was performed using the program FASTA3 (Pearson et al, Proc. Natl. Acad. Sci. USA 85:2444-2448, 1988, which is herein incorporated by reference). Numbering starts from amino acid 1 of each protein. An ":" symbol indicates an exact amino acid identity; "." indicates similar amino acids in each sequence; and "-" indicates a site at which a gap was introduced to facilitate alignment. Underlined regions indicate "P box" (30-35 in DSF) and "D box" (49-59 in DSF) regions. Both gaps in the alignment fall within the D-box. Not only is this region variant for size, it is the least similar portion of the entire region shown. The last residue of the P box (glycine at residue 35 of DSF, indicated in bold) is converted to an aspartic acid in the DSF6 mutation. Histidine at residue 24 of DSF, indicated in bold, is converted to tyrosine in the DSF7 mutation. The T box, assigned by analogy to that in Kurokawa et al. , 1993, supra, is underlined and noted. Homology extends to the end of the T box but does not enter the A box region. Figure 10 shows an alignment of a ligand binding domain of DSF protein (SEQ ID NO:4) and human tailless protein (SEQ ID NO:7). Alignment was performed using the program FASTA3 (Pearson et al. , 1988, supra). Numbering is relative to the sequence of the full length proteins. Symbols are as before. The glutamine residue (Q, underlined and bold) of the DSF sequence is converted to a terminator by the DSF1 mutation. The DSF sequence extends 9 amino acids beyond what is shown and the Human Tailless sequence extends an additional 5 amino acids beyond what is shown. Figure 11 shows a homology comparison between DSF and other nuclear receptors of the TLX/COUP class. The percentage identity of DSF to the other receptors in the DNA binding domain (DBD), hinge, and ligand binding domain (LBD) are indicated. P box sequences (SEQ ID Nos:8 to 10) and D box sequences (SEQ ID Nos:l 1 to 16) of DSF and the other nuclear receptors also are shown. Figure 12 shows the binding of DSF and dTLL (Drosophila tailless) to a pool of double-stranded DNA oligonucleotides. The pool contains a core sequence, 5'-AAGTCA-3' (SEQ ID NO: 17), common to the oligonucleotides. This core sequence is flanked on either side by 20 nucleotides that, together, form a pool of "semi-random" sequences. Binding of DSF and dTLL to this pool of semi-random oligonucleotides is approximately equal. Figure 13 shows the differential binding of in- vitro translated DSF, cTLX (chicken tailless) and dTLL (Drosophila tailless) proteins or empty expression vector (FLAG) to oligonucleotides containing direct (DRl and DR2) or inverted repeats of a consensus tailless half site sequence: 5'-AAGTCA-3' (SEQ ID NO: 17). DRl, direct repeat with one nucleotide separating the half site (SEQ ID NO: 18); DR2, direct repeat with two-nucleotides separating the half site (SEQ ID NO: 19); IR1, inverted repeat with one nucleotide separating the half site (SEQ ID NO:20). Oligonucleotide sequences are as indicated and arrows indicate the orientation of the core 5'-AAGTCA-3' (SEQ ID NO: 17) sequence. Figure 14 shows that DSF can repress gene expression on some DNA sites, similar to TLL binding sites, to which it binds. Proteins tested for repression or activation activity were DSF, chicken tailless (cTLX), Drosophila tailless (dTLL), and heterodimers of the ecdysone receptor with an appended N-terminal VP-16 activation domain (VP-16-EcR) and Ultraspiracle (USP). Possible regulatory target sites are indicated in the line labeled "reporter." "DR" denotes sites composed of two copies of the sequence 5'-AAGTCA-3" (SEQ ID NO: 17) arranged as direct repeats; the number following DR indicates the number of nucleotides separating each of the 5*-AAGTCA-3' (SEQ ID NO:17) sites. "IR1" denotes sites composed of two copies of the sequence 5'-AAGTCA-3" (SEQ ID NO: 17) arranged as inverted repeats separated by a single nucleotide. The number before each site (i.e., Ix, 2x, 3x etc.) indicates the number of times the binding site (e.g., DRl) is duplicated in the construct tested. "hsp27 EcRE" denotes the ecdysone responsive element of the Drosophila hsp27 gene. The sequences for DRl (SEQ ID NO: 18), DR2 (SEQ ID NO: 19) and IR1 (SEQ ID NO:20) are as shown in Figure 13. The mean of normalized luciferase values for three independent transient transfections into CV-1 cells are shown (solid bars); the standard deviation is indicated by thin error lines extending above the solid bars. Figure 15 shows that DSF can function as a repressor. GAL4 DNA binding domain appended to the amino terminus of DSF (GAL4-DSF) and dTLL (GAL4-dTLL) proteins were examined for repression or activation activity. Mean normalized luciferase values of three wells in shown (solid bars); the standard deviation is indicated as before. Figure 16 shows the repressive activity of several DSF-GAL4 DNA binding domain (GAL4DBD) chimeras. GAL4-DSF, GAL4-DSF hinge region (DSF H ), GAL4-DSF hinge region and ligand binding domain (DSF^), GAL4-DSF ligand binding domain (DSF L ), GAL4-dTLL and GAL4-dTLL ligand binding domain (dTLL L ). Mean normalized luciferase values and standard deviation were determined and are indicated as before. Figure 17 shows the interaction of DSF LBD with DSF, Ecdysone receptor-A (EcR-A), Drosophila tailless (dTLL) and Ultraspiracle (USP) in a GST (glutathione- S-transferase) pull down assay. GST, GST-DSF LBD , and GST-cTLX were used. Figure 18 shows three ecdysone receptor isoforms; EcR-Bl, EcR-B2 and EcR-A that have identical DBD's and LBD's, but distinct N-termini. Figure 19 shows that DSF and dTLL can function synergistically with EcR. EcR-VP16 (VP16 fused N-terminal to the EcR DNA binding domain) were used in these studies. Mean normalized luciferase values and standard deviation was determined and are indicated as before. Figure 20 shows the effect of expressing DSF, DSF LBD and dTLL on luciferase expression mediated by an ecdysone receptor with an appended N-terminal VP16 activation domain (VP16-EcR). Mean normalized luciferase values and standard deviation were determined and are indicated as before. Figure 21 shows several global and neural insect expression drivers and the expression system used for their misexpression in insects. Figure 22 shows the results of DSF and cTLX misexpression in Drosophila using various neural and global expression drivers. Figure 23 is a schematic diagram of an exemplary in vivo screen for DSF ligand agonists. Figure 24 shows the nucleic acid sequence of DSF extending from the middle of the EcoRI fragment of Figure 2 to the end of the 11.0 Kb EcoRI fragment encoding the DSF ligand binding domain (SEQ ID NO:21). Figure 25 shows the nucleic acid sequence of the 1.8 Kb EcoRI fragment of DSF large intron ("Dsf; SEQ ID NO:22). The sequence labeled "Sbjct" (SEQ ID NO:23) is the sequence as determined by the Drosophila genome project. The sequences are identical except as shown at Dsf positions 501 (Dsf=g, Sbjct=gap) and 1199 (Dsf=t, Sbjct=a). Figure 26 shows the binding of DSF and DSF fragments to the two individual half sites present in DRl . In vitro-translated FDSFp L , FDSF DI72.322 , FDSF DBD , or empty FLAG vector were incubated with equivalent labeled quantities of complete DRl direct repeat-containing oligonucleotide (left panel), an oligonucleotide containing the 5' half site of DRl (middle panel), or an oligonucleotide containing the 3' DRl half site (right panel), and binding was analyzed by EMSA. Shifted bands are indicated to the right of the figure, nonspecific bands (NS) resulting from reticulocyte lysate are indicated at left. Note that the FDSFFL-shifted band gives a weak signal on the oligonucleotides tested, and comigrates with the lower non-specific band. DETAILED DESCRIPTION OF THE INVENTION In a first embodiment, the present invention provides substantially pure DSF polypeptide. DSF polypeptide is characterized as having a predicted molecular weight of about 74,006 Da (74 kDa). DSF polypeptide is exemplified by the 692 amino acid sequence set forth in SEQ ID NO:2 (Figure 5). As used herein, the terms "substantially pure" or "isolated" refers to invention DSF polypeptides, functional fragments thereof and nucleic acids that are produced by the hand of man and are therefore separated from their native in vivo cellular environment. Generally, DSF polypeptides, functional fragments thereof and nucleic acids so separated are substantially free of other proteins, lipids, carbohydrates or other materials with which they are naturally associated. The invention further includes functional DSF polypeptides having minor modifications of and additions to the amino acid sequence of the DSF polypeptide that have a biological activity or function substantially equivalent to DSF polypeptide. Specifically disclosed herein in Table I are functional DSF polypeptides with minor amino acid sequence modifications that have substantially equivalent function. As used herein, the term "functional polypeptide" refers to a modified DSF polypeptide that possesses a biological activity or function which is identified through a functional assay. One example of a DSF biological activity is the ability to bind DNA. Another example of a DSF biological activity is the ability to bind ligand. Thus, functional assays include DNA binding and ligand binding assays. Additional DSF functions include transcriptionai activation, transcriptionai repression, the ability to bind or interact with proteins in vitro or in vivo, and the ability to be modulated by compounds. DSF biological activities include particular behavioral, biologic, morphologic, or other characteristics present in a cell, tissue or organism. For example, altered DSF or loss of DSF function, in insects, leads to abnormal sexual behavior (e.g., DSF males are bisexual and DSF females are resistant to male courtship, and are also resistant to males during copulation), biology (e.g., DSF males have significant difficulty in copulating as a result of poor performance of the abdominal bend necessary for copulation and DSF females produce normal eggs and store sperm normally, but never lay eggs), morphology (e.g., DSF males exhibit abnormal neuromuscular junctions on the ventral muscles of abdominal segment 5 and the failure of DSF females to lay eggs correlates with an absence of motor neuronal synapses on the circular muscles of the uterus) and phenotype (e.g., structural alterations in the neural cells of the abdomen). Thus, functional assays also include sexual behavior, biological function, morphology and phenotypic alterations conferred by altered DSF polypeptide or expression. Yet another biological activity of a DSF polypeptide is the ability to bind to an antibody which binds a polypeptide as set forth in SEQ ID NO:2. Thus, a modified DSF polypeptide that binds an antibody to which a polypeptide set forth in SEQ ID NO:2 binds has the requisite biological activity. Antibody binding can be tested using a variety of methods known in the art. In another embodiment, the present invention provides DSF polypeptides substantially the same as the sequence set forth in SEQ ID NO:2. The term "substantially the same," when used as a modifier of a DSF polypeptide or functional fragment thereof, means an amino acid sequence having variations from the amino acid sequence in SEQ ID NO:2, provided that the amino acid sequence retains a biological activity or function of DSF as described herein (e.g., that an antibody raised to the substituted polypeptide also immunoreacts with the unsubstituted polypeptide). Substantially the same DSF polypeptides include, for example, conservative substitutions of the amino acid sequence in SEQ ID NO:2. As used herein, the term "conservative substitution" denotes the replacement of an amino acid residue by another, biologically similar residue. Examples of conservative substitutions include the substitution of a hydrophobic residue such as isoleucine, valine, leucine or methionine for another, the substitution of a polar residue for another, such as the substitution of arginine for lysine, glutamic for aspartic acids, or glutamine for asparagine, and the like. The term "conservative substitution" also includes the use of a substituted amino acid in place of an unsubstituted parent amino acid. DSF polypeptides or functional fragments thereof substantially the same preferably share at least 75% identity with SEQ ID NO:2, more preferably, at least 85% identity with SEQ ID NO:2 and, most preferably, 90% or more identity with SEQ ID NO:2. Functional DSF polypeptides further include "chemical derivatives," in which one or more of the amino acids therein has a side chain chemically altered or derivatized. Such derivatized polypeptides include, for example, amino acids in which free amino groups form amine hydrochlorides, p-toluene sulfonyl groups, carobenzoxy groups; the free carboxy groups form salts, methyl and ethyl esters; free hydroxl groups that form O-acyl or O-alkyl derivatives as well as naturally occurring amino acid derivatives, for example, 4-hydroxyproline, for proline, 5-hydroxylysine for lysine, homoserine for serine, ornithine for lysine etc. Also included are amino acid derivatives that can alter covalent bonding, for example, the disulfide linkage that forms between two cysteine residues that produces a cyclized polypeptide. DSF polypeptide modifications may be deliberate, as by site-directed (e.g., PCR based) or random mutagenesis (e.g., EMS) or may be spontaneous or naturally occurring. For example, naturally occurring allelic variants can occur by alternative RNA splicing, polymoφhisms or spontaneous mutations of a nucleic acid encoding DSF polypeptide. Further, deletion of one or more amino acids can also result in a modification of the structure of the resultant polypeptide without significantly altering a biological activity. Deletion can lead to the development of a smaller active molecule which could have broader utility. For example, it may be possible to remove amino or carboxy terminal or internal amino acids not required for DSF activity. Alternatively, additions to the sequence may provide an additional desired functionality. All of the DSF polypeptides produced by such modifications are included herein as long as the modified polypeptide possesses at least one DSF biological activity or function as described herein. In another embodiment, the invention provides functional fragments of DSF polypeptide. As used herein, the term "functional fragment of DSF polypeptide," refers to a DSF polypeptide fragment that retains at least one biological activity or function characteristic of a DSF polypeptide as described herein. Biologically functional fragments can therefore vary in size from a polypeptide fragment as small as an epitope capable of binding an antibody molecule (i.e., about five amino acids) up to the entire length of a DSF polypeptide capable of participating in the characteristic induction or programming of behavioral and morphological changes within an organism (i.e., a wild type DSF function). Preferably, biologically functional DSF fragments are at least ten amino acid residues in length; more preferably, at least 20 amino acid residues in length; and most preferably, at least 30 amino acid residues in length. A particular example of a functional fragment of DSF is a polypeptide including from about amino acid residue 1 to 103 of SEQ ID NO:2 (Figure 6). This functional fragment includes the DNA binding domain of DSF polypeptide, which includes from about amino acid residue 8 to 94 of SEQ ID NO:2. Within the DNA binding domain of DSF are several regions that confer a biological activity (Figure 6). For example, the P box, an about six amino acid sequence, forms the DNA recognition helix that determines the preferred nucleotide half site sequences for binding (Umenso et al, Cell 57:1139-1146, 1989; Mader et al, Nature 338:271-274, 1989). Amino acids at the positions of the aspartic acid (D), Glycine (G) and Glycine (G) resides of the P box have been shown to be involved in nucleotide-specific interactions in the glucocorticoid receptor, Retinoid X Receptor (RXR) and Thyroid Receptor (TR) (Luisi et al, 1991, supra; Rastinejad et al, 1995, supra) and to be critical for distinguishing between favored binding sites for the estrogen, glucocorticoid and thyroid hormone receptors (Umesono et al, 1989, supra; Mader et al, 1989, supra). The second glycine of the P box is changed to an aspartic acid residue (D) by the DSF6 mutation. The D box, an about nine amino acid sequence, is involved in determining the spacing between the P box-binding DNA half sites favored by receptor dimers (Umesono et al, 1989, supra; Luisi et al, 1991, supra; Rastinejad et al, 1995, supra). The D box of DSF is longer than other known D boxes, suggestive of unique spacing between the DNA sites recognized by homo or heterodimers. The T box and A box sequences also are noted based on those defined in Umesono et al. , 1989, supra. The T box region of the thyroid hormone receptor has been shown to be involved in contacts with the D box region of RXR in RXR/TR dimers bound to a DR4 binding site (Luisi et al, 1991, supra; Rastinej ad et al. , 1995 , supra). By inference from the structure of RXR/TR dimers, T box amino acids of the Vitamin D Receptor (VDR) are predicted to interact with D box amino acids of RXR in RXR/VDR dimers on a DR3 binding site. A box amino acids can interact with the phosphate backbone of DNA (Rastinejad et al, 1995, supra; Fields et al, Nature 340:245-246, 1989) and, by their positioning relative to bound dimerization partners, contribute to selection of specific half site spacing or orientation (Kurokawa et al, Genes and Develop. 7:1423-1435, 1993; Rastinejad et al, 1995, supra; Fields et al, Nature, 1989, supra). Such regions of DSF that have a biological activity, when removed from a DSF polypeptide, also are included within the meaning of the term functional fragments as used herein. Another example of a functional fragment of DSF is a polypeptide including the ligand binding domain (LBD) of DSF polypeptide (Figure 7). The ligand binding domain extends from about amino acid residue 496 to 684, which is near the carboxy terminus of SEQ ID NO:2. Exemplary biological activities conferred by DSF LBD include ligand binding and repression of gene expression. Functional fragments of DSF can be identified using methods disclosed herein (e.g., by sequence homology, fragment expression studies and binding/interaction assays) as well as by site-directed mutagenesis, deletion analysis etc. of expressed DSF. For example, as disclosed herein, DSF LBD repressor activity was identified by co-expressing DSF LBD with ecdysone receptor (EcR; see e.g. , Figures 16 and 20). Functional fragments also are identified through the use of DSF chimeras. For example, DSF LBD linked to a GAL4 DNA binding domain (DBD) repressed activity of a reporter gene operatively linked to a GAL4 responsive transcriptionai regulatory element (e.g., UAS). A DSF functional fragment that confers transcriptionai activation similarly can be identified by expressing DSF fragments alone or in combination with GAL4 DBD , for example, and assaying for activity. A DSF fragment-GAL4 DBD chimera that confers gene expression upon UAS operatively linked to a reporter gene thereby identifies the DSF fragment as having an activation or transcription enhancement function. Invention functional fragments of DSF polypeptide include all modifications, amino acid substitutions, additions, deletions, insertions and derivatives set forth herein in respect to functional DSF polypeptide, provided that the functional fragment so modified retains at least one biological activity or function of DSF polypeptide as described herein. Thus, substantially the same functional fragments of DSF polypeptides can have amino acid sequence variations from an amino acid sequence fragment of SEQ ID NO:2, including, for example, conservative amino acid substitutions in a DNA binding domain fragment of SEQ ID NO:2, ligand binding domain fragment of SEQ ID NO:2, and the like. Thus, in accordance with the present invention, functional fragments of DSF polypeptide substantially the same as an amino acid sequence fragment of SEQ ID NO:2 also are provided. Substantially pure DSF polypeptides and functional fragments thereof can be obtained using standard techniques for protein purification, for example, by chromatography (e.g., ion-exchange, size-exclusion, reverse-phase, immunoaffinity etc.). Other protein purification methods known in the art additionally can be used (see e.g. , Deutscher et al. , Guide to Protein Purification: Methods in Enzymology. Vol. 182, Academic Press, 1990, which is incoφorated herein by reference). Alternatively, substantially pure DSF polypeptide and functional fragments thereof can be obtained using recombinant expression methods as disclosed herein. For example, polynucleotide encoding the protein can be produced, inserted into a vector and transformed into host cells using well known techniques described herein and further known in the art (Sambrook et al, Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, N.Y., 1989, which is incoφorated herein by reference). Following transformation, protein may be isolated and purified in accordance with conventional methods. For example, lysate prepared from an expression host (e.g., bacteria) can be purified using HPLC, size-exclusion chromatography, gel electrophoresis, affinity chromatography, or other purification technique. Substantially pure functional fragments of DSF polypeptide also can be obtained by chemical synthesis using a peptide synthesizer (e.g., Applied Biosystems, Inc., Foster City, CA; Model 430A or the like). Substantially purified protein will generally be at least about 80% pure, preferably at least about 90% pure, and may be up to 100% pure. Substantially pure DSF polypeptides or functional fragments thereof are intended to be free of other proteins as well as cellular debris and will yield a single predominant band on a non-reducing polyacrylamide gel. The purity of DSF polypeptide and functional fragments thereof can be determined, for example, by amino acid sequence analysis, chromatography (e.g., HPLC), and the like. In another embodiment, the present invention provides isolated polynucleotides encoding invention DSF polypeptides and functional fragments thereof. The DSF gene has been mapped to region 26A on the second chromosome of Drosophila melanogaster. Specifically disclosed herein is a nucleic acid sequence for Drosophila DSF (SEQ ID NO:l; Figure 9; GenBank Accession No. AF106677) that encodes a 692 amino acid DSF polypeptide set forth in SEQ ID NO:2. As used herein, the terms "polynucleotide" and "nucleic acid sequence" refer to nucleic acid, and therefore encompass DNA (genomic DNA, cDNA), RNA (e.g., mRNA), oligonucleotides, primers and probes. Invention polynucleotides include naturally occurring, synthetic, and intentionally altered or modified polynucleotides as well as splice variants. Alterations of a DSF nucleotide sequence may not change the encoded amino acid, may result in an amino acid change which is consistent with a DSF biological activity, or may result in an amino acid change that results in an alteration of at least one DSF biological activity or function as disclosed herein. Specifically included are polynucleotides having alterations in the nucleic acid sequence which still encode functional DSF. Particular examples of DSF polynucleotide alterations are polymoφhisms. As used herein, the term "polymoφhism" refers to a naturally occurring or synthetically produced (e.g., EMS induced mutagenesis) nucleotide sequence difference that may or may not produce an altered amino acid sequence. Thus, polymoφhisms can be silent such that DSF biological activity generally is comparable to unaltered DSF, or be detectable. For example, polymoφhisms that inhibit or enhance/activate a DSF polypeptide biological activity or function. Specifically disclosed herein in Table I are several DSF polymoφhisms and other sequence alterations that are silent or that result in a loss or inhibition of a DSF biological activity or function. TABLE I DSF Amino Acid and Nucleotide Changes Amino acid changes leading to loss of a biological activity: position amino acid change allele #24 H-Y dsf7 #35 G-D dsf6 #546 Q ~ stop dsfl Amino acid changes consistent with a biological activity: position alternatives #192 TorS #237 IorV #250 SorN #300 AorT #414 N or deleted #415 N or deleted Nucleotide changes leading to loss of a biological activity: position nucleotide change allele #325 C-T dsf7 #359 G-A dsfό #1891 C--T dsfl Nucleotide polymorphisms leading to amino acid polymorphisms consistent with a biological activity: position alternatives #829 AorT #964 GorA #1004 GorA #1153 GorA #1495-1497 AAC or deleted #1498-1500 AAC or deleted TABLE I DSF Amino Acid and Nucleotide Changes (Continued) Nucleotide polymorphisms not leading to amino acid changes or loss of a biological activity: position alternatives #537 GorA #567 TorC #708 TorC #729 CorT #936 CorT #940 TorC #963 GorC #1008 TorA #1059 AorC #1149 CorG #1179 CorT #1188 CorT #1218 CorT #1302 TorG #1317 Cor A #1320 AorG #1325 GorT #1389 GorA #1461 TorC #1464 CorT #1476 CorT #1482 CorT #1503 TorC #1521 CorT #1566 Cor A #1586 CorG #1713 GorA #1720 CorT #1812 GorC Altered invention polynucleotides may be intentionally altered by site-directed mutagenesis or portions of an mRNA sequence may be altered due to alternate RNA splicing patterns or the use of alternate promoters for RNA transcription. Alterations of DSF nucleic acid include but are not limited to intragenic mutations (e.g. , point mutation, splice site and frameshift) and heterozygous or homozygous deletions. Termination signals or mutations that produce a stop codon leading to a terminated DSF translation product may or may not retain a DSF biological function in vivo depending on the length of the terminated product, product stability, etc. Detection of DSF sequences having altered nucleotides can be determined by standard methods known to those of skill in the art which include, for example, sequence analysis, Southern blot analysis, PCR based analyses (e.g., multiplex PCR, sequence tagged sites (STSs) and in situ hybridization). The polynucleotides of the invention also include sequences that are degenerate as a result of the genetic code. There are 20 natural amino acids, most of which are specified by more than one codon. Degenerate sequences may not selectively hybridize to other invention nucleic acids; however, they are nonetheless included as they encode invention DSF polypeptide and functional fragments thereof. Thus, in another embodiment, degenerate nucleotide sequences that encode DSF polypeptide set forth in SEQ ID NO:2, and functional fragments of SEQ ID NO:2, are provided. The polynucleotide sequences for DSF include complementary sequences (e.g., antisense of SEQ ID NO:l) and sequences encoding dominant negative forms of DSF. Further included are double stranded RNA sequences from a DSF coding region. The use of double stranded RNA sequences (known as "RNAi") for inhibiting gene expression, for example, in insects and in other organisms is well known in the art (Kennerdell et al, Cell 95:1017-1026 (1998); Fire et al, Nature 391 :806-811 (1998)). Such sequences can interfere with DSF activity or expression. An effective amount of double stranded RNA from the coding region of DSF, DSF antisense polynucleotides and polynucleotides encoding dominant negative forms of DSF can inhibit DSF function or expression and are therefore useful in agricultural compositions, as described herein. Such invention polynucleotides can be further contained within carriers suitable for passing through a cell membrane, in vectors and can be modified so as to be nuclease resistant in order to enhance their stability or insecticidal efficacy in the agricultural compositions, for example. Thus, in another embodiment, polynucleotides encoding DSF including the nucleotide sequence set forth in SEQ ID NO: 1 (Figure 4), as well as nucleic acid sequences complementary to that sequence (e.g., antisense polynucleotides) are provided. When the invention polynucleotide sequence is RNA, the deoxyribonucleotides A, G, C, and T of SEQ ID NO:l are replaced by ribonucleotides A, G, C, and U, respectively. It is understood that DSF homologs, including DSF homologs having polymoφhisms as set forth herein, also are included. Nucleic acid probes based on SEQ ID NO:l can be used to identify such DSF homologs, for example. Homologs are envisioned to be present in living organisms that reproduce sexually including animals, such as mammals. Particular insect DSF polynucleotides include, but are not limited to the bristletail, springtail, mayfly, dragonfly, damselfly, grasshopper, cricket, walkingstick, praying-mantis, lady bug, cockroach, earwig, termite, stonefly, lice, thrip, bed bug, plant bug, damsel bug, flower bugs, assassin bug, ambush bug, lace bug, stink bug, cicada, treehopper, leafhopper, spittlebug, planthopper, aphid, whitefly, beetle, scoφionfly, caddisfly, moth, skipper, butterfly, crane fly, sand fly, mosquito, horse fly, fruit fly, house fly, bee, wasp, and ant DSF genomic and cDNA sequences. Polynucleotides encoding portions of DSF polypeptide are included herein. Particular examples are nucleic acid sequences that encode DSF functional fragments. As used herein, the term "functional polynucleotide" denotes a polynucleotide that encodes a functional polypeptide as described herein. Thus, the invention includes polynucleotides encoding a polypeptide having a biological activity of the amino acid sequence set forth in SEQ ID NO:2, for example, an epitope for an antibody immunoreactive with DSF polypeptide. Moreover, as polynucleotides having nonsense (stop) mutations in a DSF nucleic acid sequence can still encode a functional fragment of DSF polypeptide, such polynucleotides are further included. Additional polynucleotides included are polynucleotide fragments of the above-described nucleic acid sequences that are at least 15 bases in length, which is of sufficient length to permit a selective hybridization to a nucleic acid encoding the amino acid sequence set forth in SEQ ID NO:2 or functional fragments thereof. Thus, in another embodiment, fragments of SEQ ID NO: 1 ; SEQ ID NO: 1 , where T can also be U; and nucleic acid sequences complementary to SEQ ID NO: 1 that are at least 15 bases in length and that will selectively hybridize to DNA that encodes the DSF polypeptide of SEQ ID NO:2, also are provided. Polynucleotide fragments of at least 15 bases in length, which selectively hybridize to nucleic acid that encodes an amino acid sequence set forth in SEQ ID NO:2, can be used to screen for related genes in other organisms, such as mammals or insects, and are referred to herein as "probes." Invention probes additionally can have a "label" or "detectable moiety" linked thereto that provides a detection signal (e.g., radionuclides, fluorescent, chemi- or other luminescent moieties). If necessary, additional reagents can be used in combination with the detectable moieties to provide or enhance the detection signal. Such labels and detectable moieties also can be linked to invention DSF polypeptides, functional fragments, antibodies, and the compounds that modulate a DSF polypeptide activity or expression of a polynucleotide encoding DSF polypeptide disclosed herein. Hybridization refers to the binding between complementary nucleic acid sequences (e.g., sense/antisense). As is known to those skilled in the art, the Tm (melting temperature) refers to the temperature at which the binding between sequences is no longer stable. As used herein, the term "selective hybridization" refers to hybridization under moderately stringent or highly stringent conditions, which can distinguish DSF related nucleotide sequences from unrelated sequences (see e.g., the hybridization techniques described in Sambrook et al, 1989, supra). Provided the appropriate probe is available, screening procedures which rely on hybridization make it possible to isolate related nucleic acid sequences, such as a DSF homolog (e.g. , cDNA or genomic DNA), from any organism. For example, a probe can be used to screen for a human DSF ortholog from a human DNA library. Once isolated, a human ortholog can be used as a reagent to determine ifthe related sequences are involved in sexual behavior or in neural outgrowth or connectivity. In nucleic acid hybridization reactions, the conditions used in order to achieve a particular level of stringency will vary, depending on the nature of the nucleic acids being hybridized. For example, the length, degree of sequence complementarity, sequence composition (e.g., the GC v. AT content), and type (e.g., RNA v. DNA) of the hybridizing regions can be considered in selecting particular hybridization conditions. An additional consideration is whether one of the nucleic acids is immobilized, for example, on a filter. In general, the stability of a nucleic acid hybrid decreases as the sodium ion decreases and the temperature of the hybridization reaction increases. An example of moderate stringency hybridization reaction is as follows: 2 x SSC/0.1% SDS at about 37°C or 42°C (hybridization conditions); 0.5 x SSC/0.1% SDS at about room temperature (low stringency wash conditions); 0.5 x SSC/0.1 % SDS at about 42 °C (moderate stringency wash conditions). An example of high stringency hybridization conditions is as follows: 2 x SSC/0.1% SDS at about room temperature (hybridization conditions); 0.5 x SSC/0.1% SDS at about room temperature (low stringency wash conditions); 0.5 x SSC/0.1% SDS at about 42 °C (moderate stringency wash conditions); and 0.1 x SSC/0.1% SDS at about 65 °C (high stringency conditions). Typically, the wash conditions are adjusted so as to attain the desired degree of stringency. Thus, hybridization stringency can be determined, for example, by washing at a particular condition, e.g., at low stringency conditions or high stringency conditions, or by using each of the conditions, e.g., for 10-15 minutes each, in the order listed above, repeating any or all of the steps listed. Optimal conditions for selective hybridization will vary depending on the particular hybridization reaction involved, and can be determined empirically. Invention polynucleotides can be obtained using various standard techniques known in the art (e.g., molecular cloning, chemical synthesis) and the purity can be determined by polyacrylamide or agarose gel electrophoresis, DNA sequencing and the like. For example, nucleic acids can be isolated using hybridization as set forth herein or computer-based techniques which are well known in the art. Such techniques include, but are not limited to: 1) hybridization of genomic DNA or cDNA libraries with probes to detect homologous nucleotide sequences; 2) antibody screening to detect polypeptides having shared structural features, for example, using an expression library; 3) polymerase chain reaction (PCR) on genomic DNA or cDNA using primers capable of annealing to a nucleic acid sequence of interest; 4) computer searches of sequence databases for related sequences; and 5) differential screening of a subtracted nucleic acid library. Between insect species, e.g., fruit fly and ant, homologs of DSF can be identified by sequence similarity, i.e., at least 50% sequence identity between nucleotide sequences, preferably at least 60% sequence identity between nucleotide sequences, more preferably at least 75% sequence identity between nucleotide sequences and most preferably at least 80% sequence identity between nucleotide sequences. Highly homologous DSF sequences will have at least 85% sequence identity. Sequence homology is calculated based on a reference sequence, which may be a region of a larger sequence, such as a conserved motif, coding region, flanking region, etc. A reference sequence will usually be at least 18 nucleotides long, more usually at least 30 nucleotides long, and may extend to the complete sequence that is being compared. Algorithms for identifying homologous sequences that account for sequence gaps, mismatches, their length and location, are known in the art, such as BLAST (see e.g., Altschul et al., J Mol. Biol. 215:403-10, 1990). Invention polynucleotides are useful for identifying homologous sequences in other organisms. For example, when a nucleotide sequence of a region encoding DSF DNA binding domain was used as a probe to screen a Drosophila virilis genomic library (J. Posakony, University of California, San Diego), a phage was isolated that contained a 4.0 kb restriction fragment that hybridized to the DSF DNA binding domain probe. Invention polynucleotides also are useful for identifying homologous sequences and proteins in database searches. For example, when a sequence of the region encoding DSF DBD was used in a BLAST search of the Berkeley Drosophila Genome Project (http://fruitfly.berkeley.edu/blast), sequences from a PI clone containing DSF sequences were identified at the location DS08584_6_fl 0: subclone 6_fl0 from PI DS08584 (AKA dl 18), bases 10788-13904, length = 3116. Similarly, when a genomic sequence of a region encoding DSF LBD was used in a BLAST search of the same database, sequences from a PI clone containing DSF sequences were identified at the location DS08584_l_h6 (AC002585): subclone l_h6 from PI DS08584 (aka dl 18), bases 8231-11586, length = 3355 and at the location DS08584_l_g4 (AC002584): subclone l_g4 from PI DS08584 (aka dl l8), basesl 0856-13898, length = 3042. Oligonucleotide probes, which correspond to a part of a DSF sequence encoding the protein in question, can be based upon a DSF sequence, such as that set forth in SEQ ID NO: 1. Alternatively, where a nucleotide sequence is not known, oligopeptide stretches of an amino acid sequence can be used to deduce the nucleic acid sequence based on the genetic code; however, as code degeneracy must be taken into account, a mixed addition reaction of a degenerate probe population can be performed. For such screening, hybridization is preferably performed on either single-stranded nucleic acid or denatured double-stranded nucleic acid. Hybridization is particularly useful in the detection of cDNA clones derived from sources where an extremely low amount of mRNA sequences relating to the polypeptide of interest are present. In other words, by using stringent hybridization conditions directed to avoid nonspecific binding, it is possible, for example, to allow the autoradiographic visualization of a cDNA clone by the hybridization of the target nucleic acid to a single probe in the mixture which is its complete complement (Wallace et al, Nucl. Acid Res. , 9:879, 1981). Alternatively, where at least two stretches of amino acid sequence of a polypeptide is known, polymerase chain reaction (PCR) of genomic DNA or cDNA using a mixed population of degenerate probes deduced from the two stretches of amino acid sequence, can be used to amplify a related polynucleotide sequence for subsequent cloning and characterization. Another alternative for identifying similar or homologous nucleic acid sequences when the amino acid sequence is not known is to screen expressed DNA sequences. For example, among standard procedures for isolating DNA sequences of interest is by the formation of plasmid- or phage-libraries. Thus, cDNA can be derived from reverse transcription of mRNA present in donor cells and cloned into an appropriate expression phage or plasmid. When used in combination with polymerase chain reaction (PCR) technology, even rare expression products can be cloned and expressed. Lambda gtl 1 is one particular example of a phage suitable for expressing a cDNA encoding polypeptides or peptides having similar epitopes as DSF. Antibodies specific for DSF can be used to detect an expression product indicative of the presence of DSF cDNA, for example. As various types of DNA libraries from a variety of different animals and cells are commercially available or can be produced from donor cells, tissue or whole organisms using well known methods, expression screening affords the capability of identifying homologs to DSF polypeptide or fragments thereoffrom a variety of other sources. As with the DSF polypeptides and functional fragments thereof disclosed herein, polypeptides identified by such expression screening can be isolated and analyzed by standard SDS-PAGE and/or immunoprecipitation analysis and/or Western blot analysis, for example. In another embodiment, the invention provides nucleic acid sequences including a disrupted DSF gene. The term "disrupted," when used in reference to a DSF gene, means an alteration in a DSF nucleic acid such that a biological activity or function of DSF polypeptide, or DSF polypeptide expression, is altered, inhibited or eliminated. Nucleic acid alterations that produce disrupted DSF can occur in a DSF coding or non-coding sequence. An alteration in a DSF coding sequence can be, but is not limited to, a point mutation, nonsense mutation, missense mutation, splice site mutation, or a frameshift mutation. Specific, non-limiting examples of a disrupted DSF having an alteration in a coding sequence are the DSF1, DSF6 and DSF7 mutations disclosed herein (see Table I and the Examples below). The alteration also can be a deletion of a segment of a nucleic acid encoding a DSF polypeptide such that a biological activity or function of the DSF polypeptide is removed or eliminated. Alternatively, an alteration can allow for expanded (e.g., in tissues/cells that do not normally express DSF) or for increased expression, for example, through the inactivation or deletion of an expression silencer. An alteration in a DSF non-coding nucleic acid sequence (i.e., 5' and 3' non-coding flanking sequences and introns of a genomic DSF sequence) can be, for example, a point mutation or deletion. A point mutation or deletion of a transcriptionai control element conferring DSF expression can inhibit or eliminate DSF expression. Another non-limiting example is a deletion of a 3' flanking sequence that confers RNA stability. Point mutation or deletion of an intronic splice site is an additional example of a disrupted DSF gene. It is understood that alterations which produce disrupted DSF gene can be present simultaneously in coding and non-coding regions of a DSF nucleic acid sequence. Another nonlimiting example of a disrupted DSF gene is a nucleic acid encoding DSF into which another nucleic acid sequence has been inserted. A nucleic acid having such an insertion, when inserted into an endogenous DSF gene in a cell, can eliminate expression of the endogenous gene encoding DSF. In a preferred embodiment, a nucleic acid sequence including a disrupted DSF gene has a nucleic acid sequence encoding a selectable marker inserted into the DSF sequence (e.g. , neomycin, which confers resistance to G418). A selectable marker is useful for selecting or for identifying a cell and/or organism (e.g., insect) having a disrupted DSF sequence. As used herein, the term "expression control element" refers to one or more nucleic acid sequences that regulate the expression of a nucleic acid sequence to which it is operatively linked. An expression control element operatively linked to a nucleic acid sequence controls transcription and, as appropriate, translation of the nucleic acid sequence. Thus an expression control element can include, as appropriate, promoters, enhancers, transcription terminators, a start codon (e.g., ATG) in front of a protein-encoding gene. "Operatively linked" refers to a juxtaposition wherein the components so described are in a relationship permitting them to function in their intended manner. For example, a polynucleotide sequence that encodes DSF polypeptide or functional fragment thereof can be operatively linked to an expression control element such that expression of an inserted sequence contiguous thereto is under the control of the element. Alternatively, an expression control element can be in an indirect linkage with a target gene sequence. For example, as shown in Figure 21, an expression control element including an insect expression driver can be used to express GAL which, in turn, can activate a gene driven, e.g. , DSF, cTLX etc. by the GAL-responsive UAS sequence. Such indirect expression systems are specifically included herein. DSF polypeptide set forth as SEQ ID NO:2 displays temporal and tissue- specific expression in Drosophila (Finley et al, Neuron 21_: 1363-74, 1998). Specifically disclosed herein is a 1.8 Kb genomic DSF sequence flanked by EcoRI restriction enzyme sites from the large intron of a genomic DSF sequence that contains an expression control element which confers much of the DSF expression pattern. The 1.8 Kb fragment operatively linked to a nucleic acid encoding DSF, when introduced into Drosophila, partially restores egg laying function in females and transgenic insects so transformed are not killed. Thus, such invention polynucleotides are useful in producing invention transgenic insects. Such invention polynucleotides also are useful for identifying compounds that modulate expression of DSF, as described herein. Accordingly, in another embodiment, the invention provides polynucleotides containing an expression control element controlling expression of an operatively linked nucleic acid in a manner substantially similar to DSF polypeptide expression. In one aspect, the polynucleotide is a 1.8 Kb genomic DSF sequence flanked by EcoRI restriction enzyme sites having the sequence set forth in SEQ ID NO:22. In another aspect, functional polynucleotide fragments of SEQ ID NO:22 containing an expression control element controlling expression of an operatively linked nucleic acid in a manner substantially similar to DSF polypeptide expression are provided. In yet another aspect, the polynucleotide is DRl set forth in SEQ ID NO: 18. In still yet another aspect, the polynucleotide is the right hand site of DRl , 5'- AGCTTCAGAAGTCAAATAGCT-3' (SEQ ID NO:26). Such polynucleotides containing an expression control element controlling expression of a nucleic acid in a manner substantially similar to DSF polypeptide expression can be modified or altered as set forth herein, so long as the modified or altered polynucleotide controls expression of an operatively linked nucleic acid in a manner substantially similar to DSF polypeptide expression. In the present context, the term "substantially similar" means that a polynucleotide controlling expression of an operatively linked nucleic acid will confer expression of the encoded polypeptide in at least one cell of an organism which expresses endogenous DSF polypeptide and, where the encoded polypeptide is DSF, will not kill the organism. Preferably, expression of the polypeptide encoded by the nucleic acid will mimic DSF polypeptide expression in the transgenic organism, as set forth herein and in publications that describe the DSF expression pattern (see e.g., Finley et al, 1997, 1998, supra). Invention DSF polynucleotide sequences may be inserted into a vector. The term "vector" refers to a plasmid, virus or other vehicle known in the art that can be manipulated by insertion or incoφoration of a polynucleotide. Such vectors can be used for genetic manipulation (i.e., "cloning vectors") or can be used to transcribe or translate the inserted polynucleotide (i.e., "expression vectors"). A vector generally contains at least an origin of replication for propagation in a cell and a promoter. Control elements, including expression control elements as set forth herein, present within an expression vector are included to facilitate proper transcription and translation (e.g., splicing signal for introns, maintenance of the correct reading frame of the gene to permit in-frame translation of mRNA and, stop codons etc.). The term "control element" is intended to include, at a minimum, one or more components whose presence can influence expression, and can also include additional components, for example, leader sequences and fusion partner sequences. By "promoter" is meant a minimal sequence sufficient to direct transcription. Both constitutive and inducible promoters are included in the invention (see e.g. , Bitter et al. , Methods in Enzymology 153:516-544, 1987). Inducible promoters are activated by external signals or agents. Also included in the invention are those promoter elements which are sufficient to render promoter-dependent gene expression controllable for specific cell-types, tissues or physiological conditions (e.g. , the 1.8 Kb EcoRI DSF sequence and the DSF binding sequence set forth in SEQ ID NO:26 disclosed herein); such elements may be located in the 5', 3' or intronic regions of the gene. Promoters useful in the invention also include conditional promoters. A "conditional promoter" is a promoter which is active only under certain conditions. For example, the promoter may be inactive or repressed when a particular agent, such as a chemical compound, is present. When the agent is no longer present, transcription is activated or derepressed. Thus, when cloning in bacterial systems, constitutive promoters such as T7 and the like, as well as inducible promoters such as pL of bacteriophage λ, plac, ptφ, ptac (ptφ-lac hybrid promoter) may be used. When cloning in mammalian cell systems, constitutive promoters such as S V40, RSV and the like or inducible promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the mouse mammary tumor virus long terminal repeat; the adenovirus late promoter) may be used. Promoters produced by recombinant DNA or synthetic techniques may also be used to provide for transcription of the nucleic acid sequences of the invention. Mammalian expression systems which utilize recombinant viruses or viral elements to direct expression may be engineered. For example, when using adenovirus expression vectors, the DSF coding sequence may be ligated to an adenovirus transcription/translation control complex, e.g., the late promoter and tripartite leader sequence. Alternatively, the vaccinia virus 7.5K promoter may be used, (see e.g., Mackett et al, Proc. Natl. Acad. Sci. USA 79:7415-7419, 1982; Mackett et al, J. Virol 49:857-864, 1984; and Panicali et al, Proc. Natl. Acad. Sci. USA 79:4927-4931, 1982). Of particular interest are vectors based on bovine papilloma virus (BPV) which have the ability to replicate as extrachromosomal elements (Sarver et al., Mol. Cell. Biol. 1:486, 1981). Shortly after entry of an extrachromosomal vector into mouse cells, the vector replicates to about 100 to 200 copies per cell. Because transcription of the inserted cDNA does not require integration of the plasmid into the host's chromosome, a high level of expression occurs. These vectors can be used for stable expression by including a selectable marker in the plasmid, such as the neo gene, for example. Alternatively, the retroviral genome can be modified for use as a vector capable of introducing and directing the expression of the DSF gene in host cells (Cone et at., Proc. Natl. Acad. Sci. USA 81:6349-6353, 1984). High level expression may also be achieved using inducible promoters, including, but not limited to, the metallothionein IIA promoter and heat shock promoters. In yeast, a number of vectors containing constitutive or inducible promoters may be used (see e.g., Current Protocols in Molecular Biologv. Vol. 2, Ch. 13, Ed. Ausubel et al, Greene Publish. Assoc. & Wiley Interscience, 1988; Grant et al. , "Expression and Secretion Vectors for Yeast," in Methods in Enzymology. Vol. 153, pp. 516-544, Eds. Wu & Grossman, 31987, Acad. Press, N.Y.,1987; Glover, DNA Cloning. Vol. II, Ch. 3, IRL Press, Wash., D.C., 1986; Bitter, "Heterologous Gene Expression in Yeast," Methods in Enzymology. Vol. 152, pp. 673-684, Eds. Berger & Kimmel, Acad. Press, N.Y., 1987; and The Molecular Biologv of the Yeast Saccharomyces. Eds. Strathern et al, Cold Spring Harbor Press, Vols. I and II, 1982). A constitutive yeast promoter such as ADH or LEU2 or an inducible promoter such as GAL may be used ("Cloning in Yeast," R. Rothstein In: DNA Cloning. A Practical Approach. Vol.l 1, Ch. 3, Ed. D.M. Glover, IRL Press, Wash., D.C., 1986). Alternatively, vectors that facilitate integration of foreign nucleic acid sequences into a yeast chromosome, via homologous recombination for example, are known in the art and can be used. Yeast artificial chromosomes (YAC) are typically used when the inserted polynucleotides are too large for more conventional yeast expression vectors (e.g., greater than about 12 kb). In accordance with the present invention, polynucleotide sequences encoding DSF polypeptide or functional fragments thereof may be inserted into an expression vector for expression in vitro (e.g., using in vitro transcription/translation kits, which are available commercially), or may be inserted into an expression vector that contains a promoter sequence which facilitates transcription in either prokaryotes or eukaryotes (e.g., an insect cell) by transfer of an appropriate nucleic acid into a suitable cell. A cell into which a vector can be propagated and its nucleic acid transcribed, or encoded polypeptide expressed, is referred to herein as a "host cell." The term also includes any progeny of the subject host cell. It is understood that all progeny may not be identical to the parental cell since there may be mutations that occur during replication. For example, although some progeny may contain mutations in the introduced vector, such progeny are nevertheless included when the term "host cell" is used. Host cells include but are not limited to microorganisms such as bacteria, yeast, insect and mammalian organisms. For example, bacteria transformed with recombinant bacteriophage nucleic acid, plasmid nucleic acid or cosmid nucleic acid expression vectors containing a DSF coding sequence; yeast transformed with recombinant yeast expression vectors containing a DSF coding sequence; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing a DSF coding sequence; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing a DSF coding sequence; or animal cell systems infected with recombinant virus expression vectors (e.g., retroviruses, adenovirus, vaccinia virus) containing a DSF coding sequence, or transformed animal cell systems engineered for stable expression. For long-term expression of invention polypeptides in host cells, stable expression is preferred. Thus, using expression vectors which contain viral origins of replication, for example, cells can be transformed with DSF polynucleotide controlled by appropriate control elements (e.g. , promoter/enhancer sequences, transcription terminators, polyadenylation sites, etc.). Although not wishing to be bound or so limited by any particular theory, stable maintenance of expression vectors in mammalian cells is believed to occur by integration of the vector into a chromosome of the host cell. Optionally, the expression vector also can contain a nucleic acid encoding a selectable or identifiable marker conferring resistance to a selective pressure thereby allowing cells having the vector to be identified, grown and expanded. Alternatively, the selectable marker can be on a second vector which is cotransfected into a host cell with a first vector containing an invention polynucleotide. A number of selection systems may be used, including, but not limited to the heφes simplex virus thymidine kinase gene (Wigler et al. , Cell 11:223, 1977), hypoxanthine-guanine phosphoribosyltransferase gene (Szybalska et al, Proc. Natl Acad. Sci. USA 48:2026, 1962), and the adenine phosphoribosyltransferase (Lowy et al, Cell 22:817, 1980) genes can be employed in tk-, hgprt " or aprt " cells respectively. Additionally, antimetabolite resistance can be used as the basis of selection for dhfr, which confers resistance to methotrexate (Wigler et al. , Proc. Natl. Acad. Sci. USA 77:3567, 1980; O'Hare et al, Proc. Natl. Acad. Sci. USA 78:1527, 1981); the gpt gene, which confers resistance to mycophenolic acid (Mulligan et al, Proc. Natl. Acad. Sci. USA 78:2072, 1981 ; the neomycin gene, which confers resistance to the aminoglycoside G-418 (Colberre-Garapin et α/., J. Mol. Biol. 150:1, 1981); and the hygromycin gene, which confers resistance to hygromycin (Santerre et al. , Gene 30:147, 1984). Recently, additional selectable genes have been described, namely tφB, which allows cells to utilize indole in place of tryptophan; hisD, which allows cells to utilize histinol in place of histidine (Hartman et al., Proc. Natl. Acad. Sci. USA 85:8047, 1988); and ODC (ornithine decarboxylase) which confers resistance to the ornithine decarboxylase inhibitor, 2-(difluoromethyl)-DL-ornithine, DFMO (McConlogue, In: Current Communications in Molecular Biology. Cold Spring Harbor Laboratory, ed., 1987). As used herein, the term "transformation" means a genetic change in a cell following incoφoration of DNA exogenous to the cell. Thus, a "transformed cell" is a cell into which (or a progeny of which) a DNA molecule has been introduced by means of recombinant DNA techniques. Transformation of a host cell with DNA may be carried out by conventional techniques known to those skilled in the art. For example, when the host cell is a eukaryote, methods of DNA transformation include, for example, calcium phosphate co-precipitates, conventional mechanical procedures such as microinjection, electroporation, insertion of a plasmid encased in liposomes, and viral vectors. Eukaryotic cells also can be cotransformed with DNA sequences encoding DSF polypeptide or functional fragments thereof, and a second foreign DNA molecule encoding a selectable phenotype, such as the those described herein. Another method is to use a eukaryotic viral vector, such as simian virus 40 (SV40) or bovine papilloma virus, to transiently infect or transform eukaryotic cells and express the protein (see e.g., Eukaryotic Viral Vectors. Cold Spring Harbor Laboratory, Gluzman ed., 1982). When the host is prokaryotic (e.g., E. coli), competent cells which are capable of DNA uptake can be prepared from cells harvested after exponential growth phase and subsequently treated by the CaCl 2 method using procedures well known in the art. Transformation of prokaryotes also can be performed by protoplast fusion of the host cell. Invention DSF polypeptides and functional fragments thereof can be used to generate additional reagents, such as antibodies. Thus, in accordance with the present invention, antibodies that bind to a DSF polypeptide, functional fragments thereof or to antigenic fragments thereof are provided. Antibody comprising polyclonal antibodies, pooled monoclonal antibodies with different epitopic specificities, and distinct monoclonal antibody preparations, also are provided. The term "antibody" includes intact molecules as well as fragments thereof, such as Fab, F(ab')2, and Fv which are capable of binding to an epitopic determinant present in a DSF polypeptide or functional fragment thereof. Other antibody fragments are included so long as the fragment retains the ability to selectively bind with its antigen. As used herein, the term "epitope" refers to an antigenic determinant on an antigen to which the paratope of an antibody binds. Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics. Generally, epitopes have at least five contiguous amino acids. Antibodies which bind to invention DSF polypeptide can be prepared using intact DSF polypeptide or small peptide fragments thereof as the immunizing antigen. For example, as it may be desirable to produce antibodies that specifically bind to the amino- or carboxy-terminal domains of DSF, amino- and carboxy-terminal fragments of DSF can be used as the immunizing antigen. The polypeptide or peptide used to immunize an animal which is derived from translated DNA or chemically synthesized can be conjugated to a carrier protein, if desired. Such commonly used carriers which are chemically coupled to the immunizing peptide include, for example, keyhole limpet hemocyanin (KLH), thyroglobulin, bovine serum albumin (BSA), and tetanus toxoid. Monoclonal antibodies are made by methods well known to those skilled in the art (Kohler et al, Nature 256:495, 1975; and Harlow et al. Antibodies: A Laboratory Manual, page 726, Cold Spring Harbor Pub., 1988, which are incoφorated herein by reference). Briefly, monoclonal antibodies can be obtained by injecting mice with a composition comprising an antigen, verifying the presence of antibody production by analyzing a serum sample, removing the spleen to obtain B lymphocytes, fusing the B lymphocytes with myeloma cells to produce hybridomas, cloning the hybridomas, selecting positive clones that produce antibodies to the antigen, and isolating the antibodies from the hybridoma cultures. Monoclonal antibodies can be isolated and purified from hybridoma cultures by a variety of well- established techniques which include, for example, affinity chromatography with Protein-A Sepharose, size-exclusion chromatography, and ion-exchange chromatography (see e.g., Coligan et al, "Production of Polyclonal Antisera in Rabbits, Rats, Mice and Hamsters," in: Current Protocols in Immunology sections 2.7.1-2.7.12 and sections 2.9.1-2.9.3; and Barnes et al, "Purification of Immunoglobulin G (IgG)," in: Methods in Molecular Biology. Vol. 10, pages 79-104, Humana Press, 1992). Methods of in vitro and in vivo multiplication of monoclonal antibodies are well known to those skilled in the art. Multiplication in vitro may be carried out in suitable culture media such as Dulbecco's Modified Eagle Medium or RPMI 1640 medium, optionally replenished by a mammalian serum such as fetal calf serum or trace elements and growth-sustaining supplements such as normal mouse peritoneal exudate cells, spleen cells, bone marrow macrophages. Production in vitro provides relatively pure antibody preparations and allows scale-up to yield large amounts of the desired antibodies. Large scale hybridoma cultivation can be carried out by homogenous suspension culture in an airlift reactor, in a continuous stirrer reactor, or in immobilized or entrapped cell culture. Multiplication in vivo may be carried out by injecting cell clones into mammals histocompatible with the parent cells, e.g., osyngeneic mice, to cause growth of antibody-producing tumors. Optionally, the animals are primed with a hydrocarbon, especially oils such as pristane (tetramethylpentadecane) prior to injection. After one to three weeks, the desired monoclonal antibody is recovered from the body fluid of the animal. The preparation of polyclonal antibodies is well-known to those skilled in the art (see, e.g., Green et al, "Production of Polyclonal Antisera," in: Immunochemical Protocols, pages 1-5, Manson, ed., Humana Press, 1992; Harlow et al, 1988, supra; and Coligan et al, 1992, supra, section 2.4.1, which are incoφorated herein by reference). Antibodies of the present invention also can be derived from subhuman primate antibody. General techniques for raising therapeutically useful antibodies in baboons can be found, for example, in Goldenberg et al, International Patent Publication WO 91/11465, 1991, and Losman et al. nt. J. Cancer 46:310, 1990, which are hereby incoφorated by reference. Alternatively, a useful anti-DSF antibody may be derived from a "humanized" monoclonal antibody. Humanized monoclonal antibodies are produced by transferring mouse complementarity determining regions from heavy and light variable chains of the mouse immunoglobulin into a human variable domain, and then substituting human residues in the framework regions of the murine counteφarts. The use of antibody components derived from humanized monoclonal antibodies obviates potential problems associated with the immunogenicity of murine constant regions. General techniques for cloning murine immunoglobulin variable domains are described, for example, by Orlandi et al, Proc. Natl. Acad. Sci. USA 86:3833, 1989, which is incoφorated herein by reference. Techniques for producing humanized monoclonal antibodies are described, for example, by Jones et al, Nature 321:522. 1986; Riechmann et al. Nature 332:323, 1988; Verhoeyen et al., Science 239:1534. 1988; Carter et al, Proc. Natl. Acad. Sci. USA 89:4285, 1992; Sandhu, Crit. Rev. Biotech. 12:437, 1992; and Singer et al, J Immunol 150:2844, 1993, which are incoφorated herein by reference. Antibodies of the invention also may be derived from human antibody fragments isolated from a combinatorial immunoglobulin library (see e.g., Barbas et al. , Methods: A Companion to Methods in Enzymology. Vol. 2, page 119, 1991 ; Winter et al.,Ann. Rev. Immunol. 12:433, 1994, which are incoφorated herein by reference). Cloning and expression vectors that are useful for producing a human immunoglobulin phage library can be obtained, for example, from STRATAGENE Cloning Systems (La Jolla, CA). In addition, antibodies of the present invention may be derived from a human monoclonal antibody. Such antibodies are obtained from transgenic mice that have been "engineered" to produce specific human antibodies in response to antigenic challenge. In this technique, elements of the human heavy and light chain loci are introduced into strains of mice derived from embryonic stem cell lines that contain targeted disruptions of the endogenous heavy and light chain loci. The transgenic mice can synthesize human antibodies specific for human antigens and can be used to produce human antibody-secreting hybridomas. Methods for obtaining human antibodies from transgenic mice are described by Green et al, Nature Genet. 7:13, 1994; Lonberg et al, Nature 368:856, 1994; and Taylor et al., Int. Immunol. 6:579, 1994, which are incoφorated herein by reference. Invention polyclonal or monoclonal antibodies can be further purified, for example, by binding to and elution from a matrix to which the polypeptide or a peptide to which the antibodies were raised is bound. Those of skill in the art will know of various techniques common in the immunology arts for purification and/or concentration of polyclonal and monoclonal antibodies (see e.g., Coligan et al, Unit 9, Current Protocols in Immunology. Wiley Interscience, 1994, which is incoφorated herein by reference). Antibody fragments (e.g., Fab, F(ab')2, and Fv) of the present invention can be prepared by proteolytic hydrolysis of the antibody, for example, by pepsin or papain digestion of whole antibodies. In particular, antibody fragments produced by enzymatic cleavage with pepsin provide a 5S fragment denoted F(ab') 2 . This fragment can be further cleaved using a thiol reducing agent, and optionally a blocking group for the sulfhydryl groups resulting from cleavage of disulfide linkages, to produce 3.5S Fab' monovalent fragments. Alternatively, an enzymatic cleavage using pepsin produces two monovalent Fab' fragments and an Fc fragment directly. These methods are described, for example, by Goldenberg, U.S. Patent Nos. 4,036,945 and 4,331 ,647, and references contained therein, which are incoφorated herein by reference in their entireties (see also Nisonhoff et al, Arch. Biochem. Biophys. 89:230, 1960; Porter, Biochem. J 73:119, 1959; Edelman et al . Methods in Enzymology 1 :422, Academic Press, 1967; and Coligan et al. at sections 2.8.1-2.8.10 and 2.10.1-2.10.4, supra). Alternatively, antibody fragments can be prepared by expression of a nucleic acid encoding an antibody fragment in E. coli, for example. Other methods of cleaving antibodies, such as separation of heavy chains to form monovalent light-heavy chain fragments, further cleavage of fragments, or other enzymatic, chemical, or genetic techniques may also be used, so long as the fragments bind to the antigen that is recognized by the intact antibody. For example, Fv fragments comprise an association of V H and V L chains. This association may be noncovalent, as described in Inbar et al. (Proc. Natl Acad. Sci. USA 69:2659, 1972). Alternatively, the variable chains can be linked by an intermolecular disulfide bond or cross-linked by chemicals such as glutaraldehyde (e.g., Sandhu, 1992, supra,). Preferably, the Fv fragments comprise V H and V L chains connected by a peptide linker. These single-chain antigen binding proteins (sFv) are prepared by constructing a structural gene comprising nucleic acid sequences encoding the V H and V L domains connected by an oligonucleotide. The structural gene is inserted into an expression vector, which is subsequently introduced into a host cell such as E. coli. The recombinant host cells synthesize a single polypeptide chain with a linker peptide bridging the two V domains. Methods for producing sFvs are described, for example, by Whitlow et al, Methods: A Companion to Methods in Enzymology 2:97, 1991; Bird et al, Science. 242:423-426, 1988; Ladner et al, U.S. Patent No. 4,946,778; Pack et al, Bio/Technology ϋ:1271-77, 1993; and Sandhu, 1992, supra. Another form of an antibody fragment is a peptide coding for a single complementarity-determining region (CDR). CDR peptides ("minimal recognition units") can be obtained by constructing and expressing genes encoding the CDR of an antibody of interest. Such genes are prepared, for example, by using the polymerase chain reaction to synthesize the variable region from the RNA of antibody-producing cells (see e.g. , Larrick et al, Methods: A Companion to Methods in Enzvmology.2:106. 1991). It is also possible to use the anti-idiotype technology to produce invention monoclonal antibodies which mimic an epitope. For example, an anti-idiotypic monoclonal antibody made to a first monoclonal antibody will have a binding domain in the hypervariable region which is the "image" of the epitope bound by the first monoclonal antibody. Antibodies of the present invention are useful for a variety of puφoses including, for example, detecting an amount of an invention polypeptide (e.g., DSF polypeptides, functional fragments thereof, and epitopes thereof). Such methods comprise contacting a sample suspected of containing an invention polypeptide (in vitro or in vivo; in a cell or organism) with an antibody under conditions that allow binding and, detecting the presence of the antibody bound to an invention polypeptide thereby detecting the presence of the invention polypeptide. The presence of an invention polypeptide can be detected by methods well known in the art, for example, ELISA, immunohistochemical staining, flow cytometry, immunoprecipitation etc. Antibodies of the present invention also are useful for purifying DSF polypeptides, functional fragments thereof, and epitopes thereof using standard immunopurification techniques known in the art. Invention antibodies also are contemplated for use in modulating a biological activity or function of a DSF polypeptide or functional fragment thereof. For example, an antibody that binds a DSF epitope at or near a region which confers a DSF biological activity can be used to modulate that activity. Thus, an antibody or antibody fragment that binds to the ligand binding domain can inhibit binding of a natural ligand that stimulates a DSF activity and therefore function as an antagonist or, alternatively, can function as an agonist ifthe antibody or antibody fragment mimics a natural ligand and stimulates a DSF activity. Antibodies or fragments thereof that bind to a DSF DNA binding domain can be used to modulate DNA binding. Invention antibodies that modulate a biological activity or function of a DSF polypeptide or functional fragment thereof are further contemplated as agricultural compositions as described herein. In another embodiment, the present invention provides transgenic animals having invention polynucleotides. As used herein, the term "animal," when modified by the term "transgenic," refers to an organism that reproduces sexually. "Transgenic animals" can include, for example, insects and non-human mammals (e.g., mice, rats, rabbits, porcine, bovine, etc.). Preferred transgenic animals are insects. The term "transgenic animal" refers to any animal whose somatic or germ line cells bear genetic information received, directly or indirectly, by deliberate genetic manipulation at the subcellular level, such as by microinjection or infection with recombinant virus. In the present context, a "transgenic animal" does not encompass animals produced by classical crossbreeding or in vitro fertilization, but rather denotes animals in which one or more cells receive a recombinant DNA molecule. Invention transgenic animals can be either heterozygous or homozygous with respect to the transgene. The term "transgenic" as used herein further includes any animal whose genome has been altered by in vitro manipulation of the early embryo or fertilized egg or by any transgenic technology to induce a gene knockout. The term "gene knockout" as used herein, refers to the disruption of a targeted gene in vivo with a complete loss of function achieved by any transgenic technology which can produce an animal in which an endogenous gene has been rendered non-functional or "knocked out." The term "transgenic" further includes cells or tissues (/. e. , "transgenic cell," "transgenic tissue") obtained from a transgenic animal genetically manipulated as described herein, or that are produced, for example, by genetic manipulation apart from an animal (e.g., by transformation of cells or tissues in culture). Preferred transgenic animals contain the transgene integrated into germ cells. Transgenic animals having a transgene integrated into germ cells have the ability to transfer the transgene to offspring. If such offspring in fact possess some or all of the transgene, then they, too, are transgenic animals. Homologous recombination is one mechanism in which a transgene is stably inserted into the genome. Although it is further preferred that the transgene be integrated into the animal's chromosome, the present invention also contemplates the use of extrachromosomally replicating sequences containing a transgene, such as those similar to yeast artificial chromosomes. The term "insect" herein includes all insect species. The term "insect" further includes an individual insect in all stages of development, including embryonic stages. Preferably, the insects are bristletails, springtails, mayflies, dragonflies, damselflies, grasshoppers, crickets, walkingsticks, praying-mantises, lady bugs, cockroaches, earwigs, termites, stoneflies, lice, thrips, bed bugs, plant bugs, damsel bugs, flower bugs, assassin bugs, ambush bugs, lace bugs, stink bugs, cicadas, treehoppers, leafhoppers, spittlebugs, planthoppers, aphids, whiteflies, beetles, scoφionflies, caddisflies, moths, skippers, butterflies, crane flies, sand flies, mosquitoes, horse flies, fruit flies, house flies, bees, wasps, ants and fruit flies. In one embodiment, a transgenic insect having a transgene disrupting expression of a nucleic acid encoding DSF (SEQ ID NO:2), chromosomally integrated into somatic cells of the insect, is provided. In one aspect, the nucleic acid encoding DSF is set forth as SEQ ID NO: 1. In another aspect, the transgene disrupting expression of a nucleic acid encoding DSF contains a nucleic acid encoding a selectable marker. Preferred selectable markers include neomycin and hygromycin. In another embodiment, the invention provides a transgenic animal having a transgene encoding a DSF polypeptide or functional fragment thereof. In one aspect, the transgenic animal is an insect. In another aspect, the DSF polypeptide is set forth in SEQ ID NO:2. Generally, DSF misexpression in insects is lethal (Figure 22). Thus, insects transformed with a nucleic acid encoding DSF or functional fragment thereof will contain a transgene in which DSF expression is inducible, conditional, or otherwise regulatable. For example, the 1.8 kB EcoRI fragment of DSF large intron (SEQ ID NO:22) operatively linked to a nucleic acid encoding DSF or a functional fragment thereof provides appropriate expression control. Thus, insects that have or do not have a DSF phenotype associated with a biological, anatomical, moφhological or physiological change associated with altered DSF as set forth herein, can be transformed with a transgene encoding SEQ ID NO:2, for example. Transgenic insects having altered DSF so transformed can exhibit a reversal of one or more characteristics of a DSF phenotype. For example, DSF females so transformed can lay eggs. Transgenic insects so transformed that do not have altered DSF phenotype can exhibit an enhanced or pronounced DSF biological activity or function. Thus, for example, DSF transgenic female insects may have increased egg laying efficiency in comparison to non-transgenic insects. Such transgenic insects may therefore exhibit enhanced reproductive capability. Thus, in another embodiment, a transgenic insect having a transgene containing an expression control element controlling expression of an operatively linked nucleic acid in a manner substantially similar to DSF polypeptide expression is provided. In one aspect, a 1.8 Kb EcoRI fragment of DSF large intron (SEQ ID NO:22), or functional fragment thereof, operatively linked to a nucleic acid, integrated into at least one cell of the transgenic insect, is provided. In another aspect, the 1.8 Kb EcoRI fragment of DSF large intron (SEQ ID NO:22) is operatively linked to a nucleic acid encoding a reporter gene. Preferred reporter genes include β-galactosidase, luciferase, chloramphenicol acetyl transferase and green fluorescent protein. Transgenic animals can be produced by methods known in the art. For transgenic insects, generally the transgene is introduced at an embryonic stage. For example, transgenic insects of the present invention can be produced by introducing into single cell embryos invention polynucleotides, either naked or contained in an appropriate vector, by microinjection, for example, which can produce insects by P-element mediated germ line transformation (see e.g., Rubin et al, Science 218:348- 353 (1982)). Totipotent or pluripotent stem cells transformed by microinjection, calcium phosphate mediated precipitation, liposome fusion, retroviral infection or other means are then introduced into the embryo, and the polynucleotides are stably integrated into the genome. A transgenic embryo so transformed then develops into a mature transgenic insect in which the transgene is inherited in normal Mendelian fashion. Additional methods for producing transgenic insects can be found, for example, in O'Brochta et al, Insect Biochem. Mol. Biol. 26:739-753 (1996) and in Louleris et al, Science 270:2002-2005 (1995). In a preferred method, developing insect embryos are infected with a virus, such as a baculovirus (e.g., Autographa californica AcNPV), containing the desired invention polynucleotide, and transgenic insects produced from the infected embryo. The virus can be an occluded virus or a nonoccluded virus. A virus can be occluded by co infection of cells with a helper virus which supplies polyhedrin gene function. The skilled artisan will understand how to construct recombinant viruses in which the polynucleotide is inserted into a nonessential region of the baculovirus genome. For example, in the AcNPV genome, nonessential regions include the pi 0 region (Adan et al, Virology 444:782-793, 1982), the DA26 region (O'Reily et al, J Gen. Virol. 71:1029-1037, 1990), the ETL region (Crawford et al, Virology 62:2 1 '3 -27 '81, 1988), the egt region (O'Reily et al., J Gen. Virol 64:1321-1328), amongst others. Significant homology exists among particular genes of different baculoviruses and therefore, one of skill in the art will understand how to insert an invention polynucleotide into similar nonessential regions of other baculoviruses. Thus, for example, a sequence encoding a DSF polypeptide as set forth in SEQ ID NO:2 may be placed under control of an AcNPV promoter (e.g., the polyhedrin promoter). Depending on the vector utilized, any of a number of suitable transcription and translation elements, including constitutive, inducible and conditional promoters, enhancers, transcription terminators, etc. may be used in order to transcribe invention polynucleotides or express invention polypeptides. Alternatively, a transgene containing a nucleic acid sequence disrupting expression of DSF may not contain a promoter as the nucleic acid sequence need not be transcribed or translated to obtain a transgenic insect having disrupted DSF. Thus, the invention provides methods for producing transgenic insects having a disrupted nucleic acid sequence encoding DSF. The methods include introducing into the genome of an insect a nucleic acid construct, including a disrupted DSF gene, and obtaining a transgenic insect having a disrupted nucleic acid sequence encoding DSF. The invention further provides methods for producing transgenic insects having a nucleic acid encoding DSF polypeptide or functional fragment thereof. As the transgenic insects described herein having invention polynucleotides or invention polypeptides may exhibit an altered reproductive capacity, such transgenic insects can be useful, for example, in agricultural compositions. In another embodiment, the present invention provides agricultural compositions comprising invention polynucleotides, polypeptide compounds that modulate a DSF activity or expression of a DSF polynucleotide and transgenic insects. In one embodiment, an insecticidal composition contains a transgenic insect carrying a transgene comprising DNA disrupting expression of DSF and an agriculturally acceptable carrier is provided. In another embodiment, a transgenic insect carrying a transgene comprising DNA disrupting expression of a nucleic acid encoding the amino acid sequence of SEQ ID NO:2, in a manner such that these polynucleotides are stably integrated into the DNA of germ line cells of the mature insect and inherited in normal Mendelian fashion, is released into the environment. The insect can then mate with insects in the environment, such that the progeny will carry DNA disrupting expression of nucleic acid sequence encoding DSF. After two or more generations of the transgenic insects mating with the insects in the environment, altered DSF homozygous progeny insects will be produced which exhibit characteristics associated with altered DSF as described herein. In another embodiment, an insecticidal composition contains an invention polynucleotide or polypeptide that inhibits or prevents a DSF biological activity or function that is used as a component of an agricultural composition for applying to plants, plant environments, or distributed in baits to effect insecticidal control of an insect. For example, a DNA disrupting expression of DSF polynucleotide, a double- stranded RNAi molecule, an antisense DSF polynucleotide or a polynucleotide encoding dominant negative DSF, in a vector if appropriate, can be contained in an insecticidal composition. The target insect guides one of skill in the art in the selection of the agent for insect control. In still yet another embodiment, an insecticidal composition contains an invention compound that modulates DSF biological activity or expression of a DSF polypeptide. For example, DSF antagonists that inhibit DSF biological activity or expression of a DSF polypeptide can confer a DSF phenotype on an insect thereby reducing or preventing reproduction. Such antagonists can function to decrease DSF biological activity (e.g., ligand binding, DNA binding, protein binding, transcriptionai activation etc.), DSF synthesis (transcription or translation) or DSF stability (transcript or polypeptide). The invention further provides agricultural compositions that promote or activate a DSF biological activity or function which include, for example, invention compounds that modulate a DSF biological activity or function. DSF agonists that induce or activate a DSF biological activity or expression of a DSF polypeptide in insect cells not normally expressing active DSF (i.e., misexpression) are used to effect insecticidal control of an insect. Such agonists can function to increase DSF biological activity (e.g. , ligand binding, DNA binding, protein binding, transcriptionai activation etc.), DSF synthesis (transcription or translation) or DSF stability (transcript or polypeptide). In another embodiment, the agricultural composition contains a nucleic acid encoding DSF and an agriculturally acceptable carrier. In another embodiment, an agricultural composition comprises a transgenic insect carrying a transgene comprising a nucleic acid encoding DSF or functional fragment thereof operatively linked to an expression control element and an agriculturally acceptable carrier. In one aspect, a conditional promoter drives DSF expression. In another aspect, an expression control element controlling expression in a manner substantially similar to DSF polypeptide expression drives expression. As transgenic insects so transformed may have increased reproductive capability as a result of increased egg laying by females, for example, beneficial insects (e.g., those that pollinate plants or produce useful products, foodstuffs and the like, such as honeybees) and predatory insects (e.g., ladybugs, praying-mantis,' walkingsticks, assassin bugs and the like) expressing a DSF transgene or functional fragment thereof may exhibit increased proliferation. Such beneficial insects can provide increased foodstuff production or for the insecticidal control of insect pests, as appropriate. Preferably, such transgenic insects do not contain altered DSF or other genes required for normal reproductive function. The concentration of the aforementioned agricultural compositions required to be effective will depend on the type of organism targeted and the formulation of the composition and the effect on reproductive behavior or function desired (i.e., increased or decreased). For example, an insecticidally effective agricultural composition is that amount sufficient to cause a significant reduction in an insect population. By insecticidally effective" means an amount sufficient to cause a significant reduction in an insect population. The insecticidally effective concentration can be readily determined experimentally by one of skill in the art. Invention agricultural compositions must be suitable for agricultural use and dispersal in fields. Similarly, compositions for the control of insect pests must be environmentally acceptable. Generally, components of the composition must be nonphytotoxic and not detrimental to the integrity of the virus vector. Foliar applications must not damage or injure plant leaves. In addition to appropriate solid or, more preferably, liquid carriers, agricultural compositions may include sticking and adhesive agents, emulsifying and wetting agents, but not components which deter insect feeding or viral functions. It may also be desirable to add components which protect the insecticidal composition from UV inactivation, degradation or components which serve as adjuvants. Reviews describing methods of application of biological insect control agents and methods and compositions for agricultural application are available (see e.g., Couch and Ignoffo, In: Microbial Control of Pests and Plant Disease 1970-1980, Burges (ed.), chapter 34, pp. 621-634, 1981; Corke and Rishbet, ibid, chapter 39, pp. 717-732; Brockwell, In: Methods for Evaluating Nitrogen Fixation. Bergersen (ed.), pp. 417-488, 1980; Burton, In: Biological Nitrogen Fixation Technology for Topical Agriculture, Graham and Harris (eds.), pp. 105-114, 1982; Roghley, ibid, pp. 115, 127, 1982; and The Biology of Baculoviruses. Vol. II, Biological Properties and Molecular Biology, CRC Press, Inc. Boca Raton, Florida, 1986, which are incoφorated herein by reference). The invention provides methods for identifying compounds that modulate a DSF polypeptide activity or expression of a polynucleotide encoding a DSF polypeptide. The methods include incubating components containing DSF polypeptide or functional fragment thereof, or a cell expressing DSF polypeptide or functional fragment thereof, and a test compound, under conditions sufficient to allow the components to interact and, determining a DSF polypeptide activity or the expression of a polynucleotide encoding a DSF polypeptide in the presence of a test compound, thereby detecting an effect of the test compound on DSF activity or expression of a polynucleotide encoding DSF polypeptide. As used herein, the term "incubating" refers to conditions that allow the contact, binding or interaction between DSF polypeptide, functional fragment thereof or polynucleotides encoding same (including non-coding polynucleotide region(s) that regulate DSF expression) and the test compound. The term "contacting" includes in solution, in solid phase and in cells. A compound that modulates a DSF polypeptide activity or expression of a polynucleotide encoding a DSF polypeptide includes "agonists," which are compounds that stimulate or activate a DSF polypeptide activity or expression and "antagonists," which are compounds that inhibit or interfere with a DSF activity or expression. Typically, an antagonist competitively or non-competitively inhibits an agonist induced activity. An example of a competitive antagonist would be a compound that binds to DSF ligand binding domain which inhibits or prevents the binding of a ligand agonist. An example of non-competitive antagonist would be a compound that binds DSF which does not prevent or inhibit the binding of a ligand agonist. "Modulate" further includes any enzymatic interaction wherein a compound performs a biochemical modification of a DSF polypeptide. Thus, compounds that postranslationally alter DSF, such as to increase or decrease phosphorylation, ubquitination, glycosylation, proteolytic cleavage and the like are therefore included. Compounds can function either directly or indirectly to modulate DSF polypeptide activity or expression of a polynucleotide encoding a DSF polypeptide. For example, the above-describe competitive antagonist that binds DSF preventing the binding to a ligand agonist is an example of a compound that functions directly. In contrast, a compound that functions indrectly, such that DSF exhibits greater affinity for a co-activator, for example, can activate or enhance a DSF activation function while inhibiting or eliminating a DSF repressive function. Alternatively, a compound that functions indirectly to stabilize a DSF conformation, such that DSF exhibits a greater affinity for a co-repressor, for example, can activate or enhance a DSF repressive function while inhibiting or eliminating a DSF activating function. Compounds that modulate a DSF activity or expression of a polynucleotide encoding DSF are identified by determining a DSF activity or polynucleotide expression in the presence and in the absence of a test compound. DSF biological activities or DSF expression, as disclosed herein, can be determined using cell free systems, in cells and in a whole organism. For example, electrophoretic mobility shift assays (EMSA) can be used to identify a compound that modulates DSF binding to DNA. The test compound is incubated with DSF polypeptide in the presence of a DNA to which DSF binds and the ability of DSF to bind DNA is determined. The DNA binding assay can be performed in vitro with either isolated DSF, for example, or using DSF obtained from cells treated with a test compound, for example. In cells, compounds that modulate DSF binding to DNA can be identified by treating cells that express or are made to express DSF or functional fragment thereof with a test compound, and then performing in vivo footprinting analysis of a DNA region to which DSF or functional fragment thereof binds. Compounds that modulate a DSF activity or expression can be identified by detecting the expression of a reporter gene operatively linked to a DSF-responsive expression control element (i.e., functional analysis). The reporter provides a detection signal (e.g., the amount of transcript or protein product produced by the reporter gene) that corresponds to the amount of DSF polypeptide activity or expression. A compound "stimulates" a DSF activity ifthe detection signal provided by the reporter gene is increased as compared with the signal in the absence of the test compound. A compound "inhibits" a DSF activity or expression ifthe signal is decreased as compared with the signal in the absence of the test compound. For example, cells capable of expressing DSF that have an appropriate reporter gene can be treated with a test compound, and the detection signal produced in the presence and absence of the compound is determined. A DSF-responsive endogenous gene to can similarly function as a reporter in order to identify compounds that modulate a DSF activity or expression. Compounds that modulate expression of a polynucleotide encoding DSF can be identified by detecting expression of a reporter gene operatively linked to a DSF-responsive expression control element (e.g., the 1.8 Kb EcoRI region of the large intron DSF sequence as set forth in SEQ ID NO:22, DRl (SEQ LD NO: 18) and the right hand half site of DRl (SEQ ID NO:26)). Increased reporter expression in the presence of a test compound in comparison to its absence thereby identifies a compound that increases expression of a polynucleotide encoding DSF. Thus, cells that contain such a reporter gene operatively linked to a DSF-responsive expression control element can be used to identify a compound that modulates DSF expression. Chimeras comprising DSF or fragments thereof and a heterologous sequence from another protein (e.g., GAL4, VP16 DBD activation domains (AD) and the like) also can be used to identify compounds that modulate a DSF polypeptide activity in cells. Chimeras having particular DSF fragments have the additional advantage of being useful for identifying compounds that modulate activities conferred by the fragment. Such activities include DNA binding, transcriptionai activation/repression, ligand binding, protein binding, etc. Such chimeras additionally are useful for identifying a region of DSF that the compound targets. For example, to identify compounds that modulate a DSF ligand binding domain (DSF LBD ) activity, a chimera comprising DSF LBD and a GAL4 DNA binding domain (GAL4 DBD ) can be expressed in cells; a compound that modulates ligand binding activity will be detected by altering expression of a reporter gene operatively linked to a GAL4 transcriptionai response element (e.g., UAS; see Figure 23). To identify compounds that modulate DSF binding to DNA, a chimera comprising a DSF DNA binding domain (DSF DBD ) and a GAL4 transcriptionai activation domain (GAL4 AD ) can be expressed in cells; a compound that modulates DNA binding will be detected by altering expression of a reporter gene operatively linked to a DSF responsive transcriptionai response element. Polypeptide sequences from other proteins can be used to form chimeras with DSF including, for example, VP16, tailless, hormone receptors such as ecdysone receptor, retinoic acid receptor, glucocorticoid receptor, functional fragments thereof and the like. Compounds, such as ligands, that bind DSF LBD also can be identified biochemically by methods known in the art. Compounds so identified can then be tested for their ability to modulate DSF activity or expression as disclosed herein. Compounds can also be identified by their ability to modulate DSF using other functional assays, as disclosed herein. The signal provided by the reporter gene can be, for example, RNA, protein, an enzymatic activity and the like. Thus, the signal can be detected by a variety of methods known in the art, including northern analysis, RNA dot blots, nuclear run-off assays, ELISA or RIA, Western blots, SDS-PAGE alone, or in combination with antibodies that immunoprecipitate the reporter gene product. Expressed products that provide an enzymatic activity or detection signal are preferred and include, for example, β-galactosidase, alkaline phosphatase, horseradish peroxidase, luciferase, green fluorescent protein and chloramphenicol acetyl transferase. Cells contemplated for use in these methods include the cells describe herein, for example, insect cells, mammalian cells (e.g. , CV-1 , COS, HeLa and L- cells) and yeast cells. Preferred host cells do not express endogenous DSF (e.g., CV-1 cells, insect cells disclosed herein that have DSF "knocked out," etc.). As the various behavioral, biological, moφhological, phenotypical and cellular effects of altered DSF biological activity or expression in insects is disclosed herein, the effect of a test compound on each of these elements individually, or in any combination, can be conveniently determined using insects in order to identify a compound that modulates a DSF polypeptide activity or expression of a polynucleotide encoding a DSF polypeptide. Test compounds that may effect DSF activity or expression of a polynucleotide encoding DSF are found among biomolecules including, but not limited to: peptides, polypeptides, peptidomimetics, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, structural analogs or combinations thereof. Test compounds further include chemical compounds (e.g., small organic molecules having a molecular weight of more than 50 and less than 5,000 Daltons, such as hormones). Candidate organic compounds comprise functional groups necessary for structural interaction with proteins, particularly hydrogen bonding, and typically include at least an amine, carbonyl, hydroxyl or carboxyl group, preferably at least two of the functional chemical groups. The candidate organic compounds often comprise cyclical carbon or heterocyclic structures and/or aromatic or polyaromatic structures substituted with one or more of the above functional groups. Known pharmacological compounds are candidates which may further be subjected to directed or random chemical modifications, such as acylation, alkylation, esterification, amidification, etc., to produce structural analogs. Test compounds can additionally be contained in libraries, for example, synthetic or natural compounds in a combinatorial library; a library of insect hormones is but one particular example. Numerous libraries are commercially available or can be readily produced; means for random and directed synthesis of a wide variety of organic compounds and biomolecules, including expression of randomized oligonucleotides and oligopeptides, also are known. Alternatively, libraries of natural compounds in the form of bacterial, fungal, plant and animal extracts are available or can be readily produced. Additionally, natural or synthetically produced libraries and compounds are readily modified through conventional chemical, physical and biochemical means, and may be used to produce combinatorial libraries. Such libraries are useful for the screening of a large number of different compounds. A variety of other compounds may be included in the screening method. These include agents like salts, neutral proteins, e.g., albumin, detergents, etc. that are used to facilitate optimal protein-protein binding or interactions and/or reduce nonspecific or background binding or interactions. For example, reagents that improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, antimicrobial agents, etc., may be used. The mixture of components are added in any order that provides for the requisite modulation. Moreover, such test compounds additionally can be modified so as to facilitate their identification or purification. Such modifications are well known to the skilled artisan (e.g., biotin and streptavidin conjugated compounds). Incubations are performed at any suitable temperature, typically between 4 and 40°C. Incubation periods are selected for optimum activity, but may also be chosen to facilitate rapid high-throughput screening. Typically, between 0.1 and 16 hours incubation time will be sufficient. Invention compounds that modulate DSF activity or expression are useful in the agricultural compositions, such as the insecticidal compositions, as disclosed herein. The invention provides methods for isolating a protein that binds to a DSF polypeptide or functional fragment thereof. The methods include incubating at least one protein and a DSF polypeptide or functional fragment thereof under conditions sufficient to allow binding, separating bound DSF polypeptide or functional fragment thereoffrom unbound DSF polypeptide or functional fragment thereof and, isolating the bound protein. The invention further provides methods for identifying a protein that binds to DSF polypeptide or functional fragment thereof. The term "bind" includes in solution, in solid phase and in cells, and includes any binding or complex formed between a protein and a DSF polypeptide or functional fragment thereof. DSF binding proteins can be isolated using conventional biochemical methods by incubating DSF or a functional fragment thereof with protein, partially purified protein or peptide expression libraries (e.g. , using panning), fractions of cell extracts, whole cell extracts, etc. The DSF-protein complex can be separated from uncomplexed DSF polypeptide by conventional means well known to one of skill in the art. The presence of a cellular component bound to DSF can be detected by size separation or other standard methods, such as non-denaturing gel electrophoresis. For example, nucleic acid encoding DSF polypeptide or functional fragment thereof can be linked to nucleic acid encoding GST and the expressed GST- DSF chimera incubated with purified protein. Alternatively, DSF polypeptide can be covalently attached to an insoluble matrix (e.g., SEPHAROSE, SEPHACYL, SEPHADEX, and the like). Bound DSF or functional fragment thereof is then washed to remove non-specific proteins, contaminants etc. Bound protein can be separated from DSF using any of a variety of methods, for example, by adding excess free DSF or alternatively, decreasing the salt concentration in the elution buffer. The binding protein(s) can then be fractionated by gel electrophoresis (e.g., SDS-PAGE), isolated from the gel, sequenced and, if desired, identified using the methods disclosed herein and further known in the art. Ecdysone receptor-A (EcR- A) and dTLL are two exemplary proteins that bind DSF identified using a GST-DSF pull down assay (Example 5). DSF also binds ecdysone receptor-B2 (EcR-B2); DSF binding to DSF or to USP was either weak or undetectable in this GST pull down assay (Figure 17). In cells, proteins that bind DSF or functional fragment thereof can be isolated, for example, by using antibody specific for DSF to immunoprecipitate DSF in association with binding protein from cells. Cells expressing DSF or that are made to express DSF or a functional fragment thereof can be metabolically labeled by adding an amino acid containing a radionuclide (e.g. , methionine, cysteine) to the growth media. The labeled cells are lysed, immunoprecipitated with DSF antibody under conditions sufficient to allow DSF-protein binding and fractionated, for example, by SDS-PAGE, and isolated from the gel. The stringency of the immunoprecipitation conditions and/or optional wash conditions can be increased to distinguish specific binding from non-specific binding. Protein(s) that binds weakly to DSF can be isolated by subjecting cells to a chemical cross-linking agent prior to cell lysis or immunoprecipitation. Agents that selectively cross-link proteins in close proximity are known in the art and can be chosen in order to minimize non-specific cross-linking. If desired, the binding proteins so isolated can be identified using methods disclosed herein or known in the art. The invention provides methods for identifying a protein that interacts with a DSF polypeptide or functional fragment thereof in a cell. In one embodiment, the method includes obtaining a cell that expresses a DSF polypeptide or functional fragment thereof or that is made to express a DSF polypeptide or functional fragment thereof, the cell also expressing a protein suspected of interacting with the DSF polypeptide or functional fragment thereof, detecting an interaction between the DSF polypeptide or functional fragment thereof in the cell with an interaction partner, isolating the interacting protein from the cell, and identifying the protein that interacts with a DSF polypeptide or functional fragment thereof. As used herein, the term "interact" refers to an association, whether transient or stable, between a DSF polypeptide or functional fragment thereof and a protein. A protein that "binds" to DSF therefore also "interacts" with DSF. Thus, in another embodiment, a protein that interacts with a DSF polypeptide or functional fragment thereof in a cell is identified in a method for identifying a protein that binds DSF, as set forth herein. It is intended however that the term "interact" also include associations between DSF or a functional fragment thereof and a protein(s), however transient, that may not be sufficient for "binding," for example, due to weaker interactions between DSF or a functional fragment thereof and the protein(s). Interact additionally includes any enzymatic interaction wherein a protein or fragment performs a biochemical modification of DSF polypeptide or functional fragments thereof. In another embodiment, a cell expresses DSF or functional fragment thereof encoded by a first nucleic acid sequence and a suspected interacting protein encoded by a second nucleic acid. The cell additionally contains or is made to contain a gene responsive to DSF polypeptide or functional fragment thereof, for example, a reporter operatively linked to a DSF-responsive expression control element. In one aspect, the second nucleic acid encodes a chimera comprising, for example, an activation domain (e.g., VP16, GAL4) linked to a polypeptide sequence (e.g. , such as that in a library) is introduced into the cells via transformation. An interaction between DSF or functional fragment thereof and the polypeptide sequence in the chimera is detected by an increase in reporter gene expression. This is believed to be due to recruitment of the general transcription machinery by the activation domain present in the chimera to the promoter of the reporter. Thus, an increase of reporter gene expression thereby identifies a protein that interacts with a DSF polypeptide or functional fragment thereof in a cell. In yet another embodiment, a cell that does not normally express DSF is transformed with a first nucleic acid sequence containing a heterologous nucleic acid sequence encoding a chimera comprising a DSF polypeptide or functional fragment thereof and a polypeptide sequence of another protein (e.g., a DNA binding or an activation domain of GAL4, VP 16, and the like). One particular example of such a chimera is DSF linked to GAL4 DBD . The transformed cells express or are made to express a second nucleic acid encoding a protein suspected of interacting with DSF or functional fragment thereof. In one aspect, the second nucleic acid sequence comprises a heterologous sequence encoding a chimera comprising a polypeptide sequence (the "bait") linked to an activation domain (e.g. , VP 16^). In this particular example, the transformed cells also contain a GAL4 driven reporter gene (e.g., UAS). Thus, an interaction between the DSF-GAL4 DBD chimera and the "baif'sequence allows the VPlό^ linked thereto to increase reporter expression. As before, this is believed to occur by recruitment of the transcription apparatus to the reporter promoter by VP 16 AD . An increase in reporter gene expression thereby identifies a polypeptide sequence (i.e. the "bait") that interacts with DSF. As an alternative embodiment, for example, is where a first nucleic acid sequence comprises a heterologous sequence encoding DSF or functional fragment thereof alone, or in a chimera with an activation domain (e.g., a VPlό^, GAL4 AD ), and where a second nucleic acid sequence encodes a chimera comprising GAL4 DBD operatively linked to a "bait" polypeptide sequence. In the alternative embodiment, an increase in expression of a GAL4 driven reporter thereby identifies a polypeptide sequence (the "bait") that interacts with a DSF polypeptide or functional fragment thereofin a cell. As the above-described methods of the invention allow for the convenient isolation of the second nucleic acid sequence encoding the bait polypeptide sequence, the methods enable the rapid identification of polypeptides that interact with DSF polypeptide or functional fragments thereof. Moreover, as the "bait" polypeptide can be encoded by a library of nucleic acid sequences, or any other nucleic acid sequence desired, the methods provide a convenient means of screening a variety of "bait" polypeptide sequences. As the interacting proteins also are binding proteins ifthe interaction is of sufficient strength, the described methods also are applicable for isolating and/or identifying a protein that binds DSF polypeptide or functional fragments thereof. The above described methods also are applicable in identifying compounds that directly or indirectly modulate a DSF activity or expression of a polynucleotide encoding DSF; e.g., an agonist would be identified as a compound that promotes or enhances interaction between DSF and an interacting protein thereby increasing reporter expression. Whereas an antagonist would be identified as a compound that inhibits or prevents interaction thereby decreasing reporter expression. Yeast and mammalian two-hybrid cell systems are well known in the art, are commercially available and are therefore applicable in the methods for isolating and/or identifying DSF interacting proteins. Thus, the methods for identifying a protein that interacts with a DSF polypeptide or functional fragment thereof can employ yeast and mammalian cells. The invention provides methods for identifying a nucleic acid sequence that binds DSF polypeptide or functional fragment thereof. The methods include contacting at least one nucleic acid sequence with a DSF polypeptide or functional fragment thereof under conditions that allow binding, detecting binding of a nucleic acid sequence to a DSF polypeptide or functional fragment thereof, isolating the bound nucleic acid sequence, and identifying the nucleic acid sequence that binds to a DSF polypeptide or functional fragment thereof. DNA sequences to which DSF binds can be identified by either in vivo or in vitro assays. For example, DNA sequences that bind DSF or functional fragment thereof can be identified by screening oligonucleotide sequences for binding, for example, using a EMSA. Nucleic acid sequences are labeled (e.g., radionuclide, fluorescent agent etc.) and mixed with expressed DSF or functional fragment thereof. Generally, non-specific nucleic acids (e.g., poly dl/dC) are included in excess of the labeled sequences in order to minimize non-selective binding of DNA to DSF. The mixture containing DNA bound DSF complex is fractionated using non-denaturing gel electrophoresis. A "shift" of the oligonucleotide to a higher molecular weight occurs upon DSF binding to an oligonucleotide. DSF shares homology with Drosophila and human tailless (Figure 8). In particular, for example, the DNA binding domain of DSF exemplified in SEQ ID NO:2 exhibits approximately 81% homology with the DNA binding domain of human tailless sequence (Figure 9) and approximately 69% homology with Drosophila tailless. In view of the homology, DSF appears likely to bind a nucleic acid sequence with some similarity to one tailless binds. As described in Example 3 and shown in Figures 12 and 13, the binding of DSF to various DNA sequences having a core 5'- AAGTCA-3' (SEQ ID NO: 17) tailless consensus sequence was determined by mixing expressed DSF with oligonucleotides. A random population of purified oligonucleotides can be screened in order to identify a binding sequence without any preconceived notion as to what the sequence may be. Alternatively, a biased (contains particular nucleotides at predetermined positions) population of oligonucleotides can be screened for binding. In either case, the shifted band can be excised, the DNA eluted from the gel, and the DNA cloned and/or sequenced. Optionally, the eluted DNA sequence(s) can, if desired, be amplified (e.g., PCR) and the in vitro binding performed one or more times with the amplified DNA sequence product(s). By repeating the assay and amplifying DNA sequences that bind, sequences with greater selectivity for DSF can be enriched and identified. Synthesis of random or biased nucleic acid sequences can be performed by any art recognized means, including, for example, an automated synthesis apparatus. A nucleic acid sequence that binds DSF polypeptide or functional fragment thereof can be identified using binding assays in cells. For example, a nucleic acid sequence (e.g., a random or a biased population of oligonucleotides) can be inserted into a vector in which the inserted sequence is operatively linked with a reporter gene, the vector can be transformed into host cells expressing DSF, and the ability of a particular nucleic acid sequence to bind DSF or functional fragment thereof can be indicated by an increase in reporter expression. As some DNA sequences that bind DSF may not activate reporter expression, such a cell binding assay can be used in combination with in vitro DNA binding assays above to distinguish polynucleotides that bind and activate reporter expression from polypeptides that bind but do not activate expression. Such DNA sequences may in fact be repressor sequences, which are characterized as sequences that repress reporter expression in response to DSF binding. For example, as shown in Figures 14 and 15, DSF appears to repress expression of a reporter operatively linked to particular TLL sites (e.g., 4xDRl) but not others (e.g., 3xDR2). DSF-VP16 chimeras activate expression of a reporter operatively linked to 4xDRl . These studies indicate that DSF functionally binds to some element within the 4xDRl sites. Accordingly, DNA binding assays in cells additionally can distinguish repressor from activator binding sequences, if desired. Thus, the invention provides methods for identifying a nucleic acid sequence that binds DSF or functional fragment thereof. As the methods can employ a plurality of oligonucleotides, either biased or unbiased, or modified as with the other polynucleotides disclosed herein, the invention further provides methods for identifying a nucleic acid sequence that binds DSF or functional fragment thereof from a plurality of oligonucleotides. Nucleic acid identified in a method of the invention can be further evaluated, detected, cloned, sequenced, and the like, either in solution of after binding to a solid support, by any method usually applied to the detection of a specific DNA, such as PCR, oligomer restriction (Saiki et al, Bio/Technology, 3:1008-1012, 1985), allele-specific oligonucleotide (ASO) probe analysis (Conner et al, Proc. Natl. Acad. Sci. USA, 80:278, 1983), oligonucleotide ligation assays (OLAs) (Landegren et al, Science 241:1077. 1988), and the like. Molecular techniques for DNA analysis as disclosed herein and known in the art can be employed (e.g., Landegren et al, Science 242:229-237, 1988). As a nucleic acid that binds DSF polypeptide or functional fragment thereof is identified by the above-described methods, the invention further provides nucleic acid sequences that bind DSF or functional fragment thereof. Such DSF binding sequences include repressor and activator sequences. The following examples are intended to illustrate but not limit the invention in any manner, shape, or form, either explicitly or implicitly. While they are typical of those that might be used, other procedures, methodologies, or techniques known to those skilled in the art may alternatively be used. EXAMPLE 1 GENETIC AND MOLECULAR LOCALIZATION OF DISSATISFACTION This example describes genetic and transformational rescue data, the cloning of an exemplary DSF and the sequence of several exemplary functional and nonfunctional DSF mutants. To localize DSF genetically, DSF was placed in heterozygous combination with a series of deletions covering much of the second chromosome of Drosophila melanogaster (the Second Chromosome Deficiency Kit from the Drosophila Genetics Stock Center in Bloomington, Indiana (flybase.bio.indiana.edu, 1998). Df(2L)GpdhA (see Lindsley, D.L., and Zimm, G.G., The Genome of Drosophila melanogaster. San Diego: Academic Press, 1992, for descriptions of this and other deletions) failed to complement DSF, thus localizing DSF to salivary chromosome region 25E-26A on the left arm of chromosome 2 (Figure 1). Additional complementation testing showed that DSF was not complemented by Df(2L)cl7 but was complemented by Df(2L)50078a (also known as Df(2L)Gpdh78) and Df(2L)cl-h2, thus placing DSF between the right hand endpoints of Df(2L)50078a and Df(21)cl7, at the boundary of salivary chromosome regions 25F and 26A (Finley et al, 1998, supra). Based on the genetic localization, a series of cosmids containing genomic DNA from this approximate region were obtained from the European Drosophila Genome Project (Siden-Kiamos et al, Nucl Acids Res. 18:6261-6170, 1990). These were placed in ordered contigs by standard molecular methods and localized relative to the deletion breakpoints via quantitative DNA blotting of DNA from animals heterozygous for a deleted chromosome and a nondeleted chromosome and by RFLP mapping of restriction fragments disrupted by the deletions (Figure 1). A P-element (p[w + ] 13321) lying just to the right of Df(2L)cl7 was obtained from the Berkeley Drosophila Genome Project and was used to initiated a series of molecular genetic screens based on local mobilization of the P-element (Tower et al, Genetics 139:347-359, 1993; Zhang et al, Genetics 139:361-373. 1993). p[w + ] 13321 was placed in combination with a variant of the P-element transposase, Delta 2-3 (Laski et al, Cell 44:7-19, 1986) and progeny containing potential P-element insertions at new sights were identified on the basis of changes in eye color. Lines with new insertions into the DSF region were identified via "inside out PCR" (Dalby et al, Genetics, 139:757-766. 1995) coupled to a multiplex pooling strategy. P-element 79 was identified in a chromosome still containing p[w + ] 13321 and P-element 402 was identified on the second chromosome homologue of the p[w + ] 13321 -containing chromosome. To generate a deletion subdividing the DSF region, the chromosome containing both 79 and p[w + ]13321 was subjected to an additional round of mobilization by Delta 2-3 in a strategy first described by Cooley et al. (Proc. Natl. Acad. Sci. USA 87:3170-3173, 1990). From this screen Df(2L)w3, spanning from the site of element 79 to the site of p[w + ]13321, was isolated (Figures 1 and 2), thus localizing DSF to the region between 79 and the end of Df(2L)cl7. Mobilization of 402 via exposure to Delta 2-3 coupled to screening for loss of DSF function or loss of the wild type white gene encoded in 402 was used to isolate imprecise excision-generated deletions in the DSF region. These include Df(2L)dsf3, Df(2L)dsf4 and Df(2L)dsf5, all of which are mutant for DSF (Figure 2). Additional deletions extending left and right of the 402 insertion site but confined to the 30 kb EcoRI fragment containing 402 are wild type for DSF (Figure 2). The combination of wild type and mutant deletion derivatives of 402 localizes an essential component of DSF to the region of the 2.4, 0.9, 1.8, 2.1 and 4.0 kb restriction fragments deleted in Df(2L)dsf5. A screen of a cosmid library of genomic DNA in a Drosophila competent transformation vector (J. Tamkun, personal communication) identified a series of cosmids spanning the Df(2L)50078a to Df(2L)cl7 region. The 7DSP6-6 cosmid (Figure 2), when present in DSF mutant animals, gives partial rescue of all DSF phenotypes in males and females, indicating that 7DSP6-6 contains a functional DSF sequence, consistent with genetic deletion analysis. To generate additional point mutations in DSF, a screen for new female- sterile mutations mapping within Df(2L)cl7 was initiated. Males were fed ethylmethane sulfonate (EMS) essentially as described by Ashburner (Ashburner, M., Drosophila. a Laboratory Manual. Cold Spring Harbor, New York, 1989) and mated to females carrying Bl L/CyO second chromosomes (see Lindsley et al, 1992, supra, for mutant descriptions). Offspring males carrying a mutagen treated second chromosome in trans to the Bl L chromosome were individually crossed to Df(2L)cl7/CyO females to generate mutagen treated second chromosomes in trans to either Df(2L)cl7 or CyO. For each potential mutation bearing chromosome, females with the mutagen treated chromosome in trans to Df(2L)cl7 were tested for fertility and egg laying. One mutant chromosome sterile and egg laying defective in trans to Df(2L)cl7 was isolated. A stock was established from male and female sibs carrying the mutagen treated chromosome in trans to CyO. This mutation fails to complement DSF and Df(2L)dsf5, thus establishing this as a new DSF allele, DSF6. RNA expression from the DSF region is very low. As a first step toward localizing DSF, the region from the middle of 4 kb restriction fragment containing the 79 P-element to the right hand end of the 4.0 kb fragment at the right hand end of the DSF region was sequenced and scanned for potential open reading frames. Two transcription units completely to the left of Df(2L)dsf5 were identified in this way and/or by RNA blotting. Neither of these are altered by Df(2L)dsf5 and they therefore cannot be DSF. Analysis of the sequence of the 2.4 kb EcoRI fragment at the left end of Df(2L)dsf5 identifies two exons which encode the first and second zinc fingers of a nuclear receptor DNA binding domain (Figure 3). PCR screening of a cDNA library identified a cDNA with an additional 5' exon, containing an ATG initiation codon, spliced in frame into the spliced DNA binding domain exons. Analysis of the sequence of the right hand 4.0 kb fragment of Df(2L)dsf5 reveals an exon encoding the T/A box region that follows directly after the DNA binding domain, as well as two exons encoding a nuclear receptor ligand binding domain followed by a termination codon. To determine if this nuclear receptor encoding gene corresponds to DSF, the identified exons encoding the nuclear receptor were PCR amplified from DSF1 and DSF6 mutant genomic DNA as well as from control wild type DNAs derived from DSF sibling chromosomes. DSF1 differs from its wild type counteφart by a single C to T change in the region encoding the ligand binding domain. This is consistent with an EMS induced mutation and changes a CAA glutamine codon to a TAA stop codon. This nonsense mutation truncates the carboxy terminal 147 amino acids, including nearly the entire ligand binding domain and should be a null or extreme hypomoφhic mutation. DSF6 differs from its wild type counteφart by a single G to A change in the region encoding the DNA binding domain. This is consistent with an EMS- induced mutation and changes a GGT glycine codon to a GAT aspartic acid codon. The altered amino acid is one of three known to determine DNA binding site specificity for nuclear receptors and to interact directly with the major groove of DNA (Luisi et al, Nature 352:497-505, 1991; Mader et al, Nature 338:271-274. 1989; Rastinejad et al, Nature 375:203-211, 1995; Umesono et al, 1989, supra). No known natural nuclear receptor has aspartic acid at this position. This must be a strong mutation. DSF7 was obtained by screening a collection of EMS-mutagenized Drosophila stocks (Charles Zuker, University of California at San Diego) for mutations that resulted in female sterility. Each of these mutations derived from mutagenized second chromosomes was tested for complementation with various dsf alleles, including dsfl . dsf7 was initially identified as a mutation which failed to complement dsfl . Direct DNA sequencing of PCR products of DNA derived dsf7/deletion DNA revealed a single C to T transition, consistent with EMS mutagenesis, in the region encoding the first finger of the DNA binding domain. This nucleotide change results in an amino acid change from histidine to tyrosine at position 24. The genetic data, the transformational rescue data, and the sequence of the mutant DNA are all consistent with each other and with the conclusion that the nuclear receptor-encoding gene within Df(2L)dsf5 is DSF. EXAMPLE 2 NATURE OF THE DSF PROTEIN This example describes several domains of DSF and their predicted function. This example also describes sequence homologies between DSF and tailless. The sequence of DSF DNA binding domain (DBD) plus T box and A box regions is shown in Figure 6 (SEQ ID NO:3). The sequence of the ligand binding domain (LBD) is shown in Figure 7 (SEQ ID NO:4). Using the BLASTP program, the sequences of the DBD and surrounding amino acids, and the LBD region were used as query sequences against the Genbank nonredundant coding sequence data base (Altschul et al, 1990, supra). Both sequences returned the human Tailless protein (Accession No. e332319) as the top scoring sequence, with a smallest sum probability of 2.6 x 10 "45 for the DNA binding domain and 1.5 x 10 "43 for the ligand binding domain. The positions of these domains and the relative identities are shown schematically in Figure 6. Gapped alignments for the DBD and LBD regions were generated using the fasta program (Pearson et al. , Proc. Natl. Acad. Sci. USA 85:2444-2448, 1988), and are shown in Figures 7 and 8. The DSF DBD region shows approximately 81% identity to the human tailless protein, with key regions of difference. The first of these is in the D box. The D box is a region of the protein bounded by the first of two cysteine residues of the second zinc finger. This is involved in determining half site spacing preferences for receptor complexes that bind as dimers (Luisi et al, 1991, supra; Perlmann et al, Genes Dev. 7:141-1422, 1993; Rastinejad et al, 1995, supra; Umesono et al, 1989, supra). A major fraction of D box regions contain 3 or 5 amino acids between the cysteine residues. Human and Drosophila tailless proteins contain 7 residues between the cysteines while DSF contains nine intervening residues. In addition, the amino acids of the DSF D box are substantially different from those of the tailless D box. The difference is not just the addition of two amino acids to otherwise similar sequences. Since vertebrate tailless protein can form dimers on sequences not selected for favoring dimerization (Yu et al, Nature, 370:375-379, 1994) it is likely that some vertebrate tailless function involves dimerization. The major differences in the D box between DSF and tailless strongly suggest that DSF-containing dimers will differ in their half site spacing preferences from Tailless dimers. Homology between DSF and tailless in the DBD extends through the T box region but does not include the A box. The human and Drosophila tailless proteins show homology that extends not only through the T box, but through the A box as well. In other systems, the A box has been shown to influence hetero and homodimer binding to particular half site combinations and to alter the ability to discriminate between different orientations of pairs of half sites (Kurokawa et al, Genes andDevel. 7:1423-1435, 1993; Rastinejad et al, 1995, supra). Thus, the differences between DSF and tailless sequences in the A box indicate differences in choice of preferred DNA binding sites and gene targets. Homology between ligand binding domains extends throughout the LBD region, with some areas having stronger identity than others. Overall identity in the LBD is 44%, with some regions showing substantially higher identity. For example, the region from amino acids 332 to 380 of human Tailless is 71% identical to the related region of DSF. The homology between DSF and tailless is consistent with both conserved functions and divergent functions. For example, the vertebrate Retinoid X Receptors (RXR) and the Drosophila RXR (Ultraspiracle, Usp) show a similar level of amino acid identity (Oro et al, Nature, 347:298-301, 1990). Usp will substitute for RXR in forming heterodimers with various vertebrate receptors (Yao et al, Cell 71 :63-72. 1992), but will not respond to the RXR ligand 9-cis retinoic acid (Oro et al, Development 115 :449-462, 1992). In reverse, the vertebrate RXR does not interact as well as Usp with the natural Usp dimerization partner the ecdysone receptor (Yao, Nature 366:476-479, 1993; Yao et al, 1992, supra). Thus, it is quite likely that DSF will respond to a ligand different from those used in mammalian systems. EXAMPLE 3 DSF BINDING TO DNA This example describes the binding of DSF to DNA in vitro. Electrophoretic mobility shift assays were performed essentially as described (Yu et al, 1994, Nature, 370: 375-379). Briefly, DSF, cTLX or dTLL proteins were produced in vitro using the TNT coupled transcription/translation rabbit reticulocyte lysate expression system (Promega, Madison WI). Complementary olignucleotides containing TLX half sites were prepared and annealed, leaving a four-base overhang, which was radiolabelled using Klenow and [32P]-dCTP. 1-4 μl in vitro-translated proteins were added to ~50,000 cpm labeled oligonucleotide in a 20 μl reaction volume, containing IX binding buffer (4 mM Tris-Cl, pH 7.5; 0.05 mM EDTA; 5% glycerol; 0.1% NP-40; 100 mM KCl; 30 ng/ μl poly dl-dC/dl-dC; 100 μM DTT). Binding reactions were incubated on ice for 30 minutes, then loaded on a 5% polyacrylamide/ 0.25x TBE gel. Gels were run at 100V for two hours, then dried onto 3mm paper and exposed to film. As shown in Figure 12, DSF appears to preferably bind semi-random TLX oligonucleotides having the core sequence 5'- AAGTCA-3 1 (SEQ ID NO: 17) flanked on both sites by 20 nucleotides of random sequence instead of to TLX-optimized binding repeats. Tailless (cTLX or dTLL) binds DRl, DR2 and IR1 of the core 5'- AAGTCA-3' (SEQ ID NO:17) sequence (Figure 13). In contrast, DSF preferably binds to a single TLX direct repeat DRl, but not to DR2 or IR1 (Figure 13). DRl differs from DR2 and IR1 in the sequence 3' to the second half site of DRl such that the sequence of DRl is 5'-CAGAAGTCA-3' (SEQ ID NO:24) whereas the DR2 and IR1 sequences only have 5'-AAGAAGTCA-3* (SEQ ID NO:25). The fact that a C is present in the first 5' position of DRl whereas an A is present at the first 5' position of DR2 and IR1 may account for the observed binding differences between DSF and tailless. dTLL and cTLX bind inverted repeat sequences and direct repeat sequences, respectively, of the 5'-AAGTCA-3' (SEQ ID NO:17) half site (Figures 13 and 14), as well as some monomers containing the 5'-AAGTCA-3' (SEQ ID NO: 17) site. Binding studies of DSF to the left and right hand sites of the DRl oligonucleotide were determined by gel shift analysis, and indicate that DSF can distinguish between two closely related sequences (Figure 26). Briefly, the two DNA half sites of the DRl to which DSF binds were separated into individual monomer binding sites and examined for binding to in vitro translated full length (FL) or DSF fragments (FDSF FL , FDSF D]72 . 322 , FDSF DBD ) and FLAG. Both a DSF modified by removal of the hinge region amino acids 172-322 (FDSF DI72.322 ) and a DSF DNA binding domain (including amino acids 1-161; FDSF DBD ) bind to DRl (SEQ ID NO: 18), but poorly bind the left hand site, 5'-AGCTAAGAAGTCAGAAGCT-3' (SEQ ID NO:27) while binding well to the right hand site, 5'- AGCTTCAGAAGTCAAATAGCT-3' (SEQ LD NO:26). The data indicate that DSF binds to DRl as a monomer, and that DSF can distinguish between potential binding sites on the basis of sequence differences outside the core half site. Since the difference between the DRl and DR2 oligonucleotides is in the region between the two core half sites, these binding data indicate that the DSF DNA binding domain and flanking regions can distinguish sites based on 5' flanking sequences. EXAMPLE 4 DSF EXPRESSION VECTORS AND DSF-GAL4 CHIMERAS This example describes the construction of the DSF expression vectors and the DSF-GAL4 chimeras and expression vectors used in the studies described herein. The original full-length DSF cDNA was constructed by a three-piece ligation, fusing: (1) a vector backbone (pBS-SK+) plus the DSF DBD ("BS-DSFDBD"), cut with BstEII (internal site 3' of DSF'sDBD) and Xhol (in pBS-SK+); (2) a genomic fragment containing DSF's hinge region, cut with BstEII and AlwNI; and (3) a PCR-generated clone containing DSF'sLBD ("BS-LPCR"), cut with AlwNI and Xhol. The two PCR- generated pieces (1 and 3) were completely sequenced prior to the ligation, and exactly match the dsf genomic sequence. The resultant full-length construct is referred to as BS- DSF^ Mammalian expression vectors were constructed using either pCMX (a gift from C.C. Tsai and R.M. Evans) or pcDNA3-FLAG ("pcFL"). pcFL is a derivative of pcDNA3 (Invitrogen), containing a FLAG epitope tag-encoding sequence at the 5' end of the multiple cloning site. This vector allows either in vitro transcription/translation (via T7) or expression in mammalian cells, under the control of the CMV promoter. A FLAG-tagged full-length DSF expression vector (pcFL-DSF fL , or FDSF FL ) was generated by cloning a BamHI-XhoI DSF fragment from BS-DSF FL into the BamHI and Sail sites of pcFL. A full-length dTLL cDNA was produced by PCR (using CMX- dTLL as a template, a gift from C.C.Tsai and R.M.Evans), introducing a 5' BamHI site and a 3* Kpnl site. This was subcloned into pBS-SK+ (BS-dTLL). A BamHI-Kpnl fragment of BS-dTLL cloned into the BamHI and Kpnl sites of pcFL to generate FdTLL. EcoRI and Sail sites were introduced 5' and 3' of full-length chicken tailless (cTLX), and the PCR product was cloned into pBS-SK+ (BS-cTLX). A BamHI-Sall fragment of BS- cTLX was cloned into pcFL to produce FcTLX. In vitro-translated pCMX-dTLL and FdTLL have identical DNA-binding ability, and transiently-transfected pCMX-dTLL and FdTLL are indistinguishable in reporter assays, indicating the FLAG epitope does not affect protein function. FDSF, FcTLX and FdTLL (or pCMX-dTLL) were used in all reporter assays using tailless (TLX) site-based reporters (Figure 14), and for in vitro translation (Figure 13). CMX-VP 16-EcR (an N-terminal fusion of VP 16 activation domain to EcR) and CMX-USP were used to express VP16-EcR and USP in transient transfections. Both were gifts from C.C.Tsai and R.M.Evans. All DSF-GAL4 chimeras were constructed using either pSG424 (Sadowski et al, Nucleic Acids Res. 17: 7539, 1989) or pCMX-GAL4 (a gift from C.C.Tsai and R.M. Evans). Both vectors drive expression of GAL4 fusions in mammalian cells, pSG424 through the SV40 early promoter, pCMX-GAL4 through the CMV promoter. GAL4-DSF contains a full-length EcoRI-Xbal DSF cDNA fragment from pcFL-DSF fL cloned into the EcoRI and Xbal sites of pSG424. GAL4-DSF H was constructed by first cloning a 1.0 Kb Notl-Sacl genomic fragment containing DSF's hinge into pBS-SK+ (BS-DSF H ), then inserting an EcoRI-SacI fragment from BS-DSIfr into the EcoRI and Sad sites of pSG424. GAL4-DSF HL was constructed by cloning a Notl-Xbal fragment of full-length DSF into pcFL (out of frame) to create the intermediate construct pcFL- DSF JJLX , then cloning a Kpnl-Xbal fragment from this vector into the Kpnl and Xbal sites of pSG424. GAL4-DSF L inserted a BamHI fragment of pBS-FdsfLPCR (containing the entire DSFLBD) into the BamHI site of pCMX-GAL4. EXAMPLE 5 DSF TRANSCRIPTIONAL EFFECTS AND BINDING TO OTHER PROTEINS This example describes the effect of DSF on transcription in cells and the binding/or interaction of DSF with other proteins in vitro and in cells. Luciferase reporter assays were performed as described (Zelhof et al, Mol Cell Biol. 15:6736-6745, 1995). CV-1 cells were seeded in 48-well plates 24 hr prior to transfection. Cells were transiently transfected by incubating 15 μl DNA (150 ng each expression vector, 600 ng luciferase reporter, and 1.5 μg CMX-lacZ, as a control for transfection efficiency) plus 15 μl DOTAP transfection reagent (prepared by H. Juguilon) at room temperature for 10 minutes, then mixing with 600 μl medium. 200 μl of each mixture was added to each of three wells. Transfections were incubated at 37°C for 48 hr, then assayed for luciferase and β-gal activity. Luciferase activity was normalized to β-gal values; the means of normalized values for three wells are shown in Figures 14 to 16, 19 and 20. To show fold activation or percent repression, data from DSF-transfected cells were compared to those transfected with an empty expression vector (pCMX or pCMX-GAL4). CV-1 cells transiently co-transfected with the luciferase reporter driven by various TLL binding site oligonucleotide sequence repeats in the presence or absence of DSF, cTLX, dTLL and VP16-EcR + USP were assayed for luciferase activity. As shown in Figure 14, full length DSF can repress expression well at DNA sites to which DSF binds well, but not at other sites to which it binds poorly (compare 4xDRl to the remaining sites in Figure 14). In contrast, dTLL and cTLX bind well to all elements but the hsp27 EcRE and appear to repress on all elements to some degree. CV-1 cells transiently co-transfected with the luciferase reporter driven by five GAL4UAS sequences and either GAL4, a GAL4-DSF chimera or a GAL4-dTLL chimera were assayed for luciferase activity. As shown in Figure 15, repression by a DSF-GAL4 chimera appears to be a weaker repressor than a dTLL-GAL4 chimera (Figure 15). Thus, DSF and dTLL differ with respect to their repressive activity. CV-1 cells transiently co-transfected with the luciferase reporter driven by five GAL4UAS sequences and either GAL4, or various GAL4-DSF chimeras, were assayed for luciferase activity. As shown in Figure 16, DSF confers repressive activity whereas the DSF hinge region does not appear to confer repressive activity. DSF ligand binding domain, in the absence or presence of the hinge region, is a more potent repressor than full length DSF. In vitro studies of protein-protein interactions were performed using a GST pull-down assay (Heinzel et al, Nature 387:43-48, 1997). All GST fusion constructs used the pGEX-KG vector (Pharmacia). GST-DSF FL was produced by inserting a BamHI-Sall fragment from BS-DSFp L into the BamHI and Sail sites of pGEX-KG. GST-DSF LBD was generated by inserting a BamHI-EcoRI fragment from BS-LPCR into pGEX-KG's EcoRI and BamHI sites. For GST-cTLX, a BamHI-Sall fragment from BS-cTLX was cloned into the BamHI and Sail sites of pGEX-KG. GST (from an empty pGEX-KG vector), GST-DSF LBD , and GST-cTLX were used in Figure 17. GST-fusion proteins were produced in BL21 bacteria. Bacteria were induced with 0.1 mM IPTG for 3-5 hours at room temperature, then lysed by sonication. GST-fusion proteins were purified on glutathione-agarose beads as described (Kaelin et al, Cell 70:351-364, 1992). Equivalent amounts of GST, GST-DSF or GST-cTLX proteins were mixed with [35 s ]-labeled, in vitro-translated DSF, EcRA (ecdysone receptor), dTLL and USP proteins (TNT system, Promega, Madison WI), as indicated. Beads were pre-incubated in 100 μl PPI (20 mM TrisaCl pH 7.9; 100 mM NaCl; 1 mM EDTA; 4 mM MgCl 2 ; 1 mM DTT; 0.02% NP-40; 10% glycerol)+ BSA (1 mg/ml) + 0.5 mM PMSF, and rotated at room temperature for 20 min. Binding reactions contained 20 μl beads, 10 μl labeled in vitro translated protein, plus 65 μl PPI + BSA + PMSF. Binding reactions were incubated at room temperature for 20 min, with mixing. The beads were subsequently washed four times in 1 ml PPI (without BSA or PMSF), then boiled for 3 minutes in 20 μl 2X SDS-PAGE loading buffer. Supematants (containing retained labeled proteins) were fractionated on a 10% SDS-PAGE, dried onto 3mm paper and exposed to film. As shown in Figure 17, DSF can bind ecdysone receptor and cTLX, but does not appear to form homodimers. To determine the effect of DSF on EcR-mediated expression, CV-1 cells were co-transfected as described before with an hsp27 EcRE-tk-luciferase reporter in combination with EcR-VP 16, DSF, DSF LBD and dTLL in various combinations. As shown in Figures 19 and 20, DSF can synergize EcR transactivation of the reporter; EcR is more highly ligand responsive in the presence of DSF (see EcR-VP 16 in the presence and absence of DSF) and increases ligand-independent EcR activity in the presence of USP (see EcR-VP 16 + USP in the presence and absence of DSF). In contrast, as shown in Figure 20, DSF LBD represses EcR transactivation (see VP16-EcR in the presence and absence of DSF LBD ). These findings are consistent with the repressive effect of DSF LBD described in Example 5. EXAMPLE 6 DSF MISSEXPRESSION This example shows that missexpression of DSF in insect cells leads to death. Transgenic insects that ectopically express DSF and cTLX were obtained using the GAL4-UAS system (Figure 21 ; Brand et al., Development 118:401-405. 1993). All in vivo DSF misexpression constructs utilized the pUAST vector (Brand et al, Development 118:401-405. 1993), for GAL4-dependent expression in Drosophila. pUAST-DSFpx. contains an EcoRI-Sall full-length DSF cDNA, from BS-DSF^, cloned into the EcoRI and Xhol sites of PUAST. For pUAST-FcTLX, a HindfLI-Apal fragment from FcTLX was cloned into pBS-SK+ (BS-FcTLX), then a Notl-Kpnl fragment of BS-FcTLX was inserted into pUAST. The constructs, along with Delta 2,3 transposase, were injected into 0-1 h wl 118 Drosophila embryos. Transgenic founder adults were mated to wl 118 flies, and transmission of the transgene was scored by the presence of eye color (carried by a mini-white gene in pUAST) in the progeny. In this manner, one UAS-FcTLX and four individual UAS-DSF transgenic lines were established, and maintained as homozygotes. To ectopically express either DSF or cTLX, these lines were crossed to the indicated GAL4 driver lines. The results shown in Figure 22 indicate that DSF mis-expression with every expression driver is embryonic lethal. cTLX mis-expression also is lethal; however, cTLX expression conferred by the neural 164 driver is lethal in the late pupal or adult stage. These results further confirm the different biological functions of DSF and tailless. Although the invention has been described with reference to the presently preferred embodiments, it should be understood that various modifications can be made without departing from the spirit of the invention. Accordingly, the invention is limited only by the following claims.

Claims: What is claimed is: 1. Substantially pure dissatisfaction (DSF) polypeptide, or a functional fragment thereof. 2. The polypeptide of claim 1, characterized as: a) having a molecular weight of approximately 74 kD, as determined by SDS-PAGE; b) being expressed in the nervous system; and c) mapping to Drosophila chromosome region 26A. 3. The polypeptide according to claim 1 , wherein the amino acid sequence of said polypeptide is substantially the same as the amino acid sequence set forth in SEQ ID NO:2 (Figure 5). 4. The polypeptide according to claims 1 or 3 comprising a sequence having at least 10 amino acids. 5. The polypeptide according to claim 1, wherein the amino acid sequence is set forth in SEQ ID NO:2 (Figure 5). 6. The polypeptide according to claim 1 , wherein said fragment is selected from the group consisting of: DNA binding domain, ligand binding domain, T box, T/A box, D-box and P-box. 7. An isolated polynucleotide encoding the DSF of claim 1. 8. An isolated polynucleotide selected from the group consisting of: a) SEQ ID NO: 1 (Figure 4) b) SEQ LD NO: 1 , wherein T can also be U; c) nucleic sequences complementary to SEQ ID NO: 1 ; and d) fragments of a), b) and c) that are at least 15 bases in length and that will selectively hybridize to DNA which encodes the DSF polypeptide of SEQ ID NO:2 under moderately stringent conditions. 9. A vector including the polynucleotide of claims 7 or 8. 10. The vector of claim 9, wherein the vector is a plasmid. 11. The vector of claim 9, wherein the vector is a viral expression vector. 12. A host cell containing the vector of claim 9. 13. The host cell of claim 12, wherein the cell is prokaryotic. 14. The host cell of claim 12, wherein the cell is eukaryotic. 15. The host cell of claim 14, wherein the cell is an insect cell. 16. An insecticide composition selected from the group consisting of: a DSF antisense, a DSF RNAi molecule and a nucleic acid encoding dominant negative DSF in an agriculturally acceptable carrier. 17. An antibody which binds to the polypeptide of claim 1 , or binds to an antigenic fragment of said polypeptide. 18. The antibodies of claim 17, wherein said antibodies are monoclonal. 19. The antibodies of claim 17, wherein said antibodies are polyclonal. 20. A transgenic insect having a transgene disrupting expression of a nucleic acid encoding the amino acid sequence of SEQ ID NO:2, chromosomally integrated into the germ cells of the insect. 21. The transgenic insect of claim 20, wherein the insect is selected from the group consisting of bristletails, springtails, mayflies, dragonflies, damselflies, grasshoppers, crickets, walkingsticks, praying-mantises, lady bugs, cockroaches, earwigs, termites, stoneflies, lice, thrips, bed bugs, plant bugs, damsel bugs, flower bugs, assassin bugs, ambush bugs, lace bugs, stink bugs, cicadas, treehoppers, leafhoppers, spittlebugs, planthoppers, aphids, whiteflies, beetles, scoφionflies, caddisflies, moths, skippers, butterflies, crane flies, sand flies, mosquitoes, horse flies, fruit flies, house flies, bees, wasps, and ants. 22. An insecticide composition comprising the transgenic insect of claim 20 and an agriculturally acceptable carrier. 23. A nucleic acid construct comprising a disrupted DSF gene, such that the disruption prevents expression of functional DSF polypeptide. 24. The construct of claim 23, wherein the disruption is by insertion of a selectable marker sequence into said gene. 25. A host cell containing the DNA construct of claim 23. 26. The host cell of claim 23, wherein the cell is an insect cell. 27. A method for producing a transgenic insect having a disrupted nucleic acid sequence encoding DSF comprising: a) introducing into the genome of an insect to obtain a transformed insect the nucleic acid construct of claim 23; and b) obtaining a transgenic insect having a disrupted DSF encoding nucleic acid sequence. 28. The method of claim 27, wherein the insect is selected from the group consisting of bristletails, springtails, mayflies, dragonflies, damselflies, grasshoppers, crickets, walkingsticks, praying-mantises, lady bugs, cockroaches, earwigs, termites, stoneflies, lice, thrips, bed bugs, plant bugs, damsel bugs, flower bugs, assassin bugs, ambush bugs, lace bugs, stink bugs, cicadas, treehoppers, leafhoppers, spittlebugs, planthoppers, aphids, whiteflies, beetles, scoφionflies, caddisflies, moths, skippers, butterflies, crane flies, sand flies, mosquitoes, horse flies, fruit flies, house flies, bees, wasps, and ants. 29. A transgenic insect having a transgene encoding the amino acid sequence of SEQ ID NO:2, operatively linked to a conditional promoter, chromosomally integrated into the germ cells of the insect. 30. The transgenic insect of claim 29, wherein the insect is selected from the group consisting of bristletails, springtails, mayflies, dragonflies, damselflies, grasshoppers, crickets, walkingsticks, praying-mantises, lady bugs, cockroaches, earwigs, termites, stoneflies, lice, thrips, bed bugs, plant bugs, damsel bugs, flower bugs, assassin bugs, ambush bugs, lace bugs, stink bugs, cicadas, treehoppers, leafhoppers, spittlebugs, planthoppers, aphids, whiteflies, beetles, scoφionflies, caddisflies, moths, skippers, butterflies, crane flies, sand flies, mosquitoes, horse flies, fruit flies, house flies, bees, wasps, and ants. 31. A method for producing a transgenic insect having a DSF encoding nucleic acid comprising: a) introducing into the genome of an insect to obtain a transformed insect, a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:2, operatively linked to a conditional promoter which functions in insect cells to cause the production of an RNA sequence; and b) obtaining a transgenic insect having a DSF encoding nucleic acid. 32. A method for identifying a compound that modulates a DSF polypeptide activity or expression of a polynucleotide encoding a DSF polypeptide, comprising: a) incubating components comprising a test compound, and a DSF polypeptide or functional fragment thereof, or a cell expressing a DSF polypeptide or functional fragment thereof, under conditions sufficient to allow the components to interact; b) determining a DSF polypeptide activity or expression of a polynucleotide encoding DSF polypeptide in the presence and absence of a test compound, thereby detecting an effect of a test compound on said DSF polypeptide activity or expression of a polynucleotide encoding DSF polypeptide; and c) identifying a compound that modulates said DSF polypeptide activity or expression of a polynucleotide encoding DSF polypeptide. 33. An insecticidal compound identified by the method of claim 32. 34. The method of claim 32, wherein said compound is from a library of compounds. 35. The method of claim 32, wherein said compound binds to the ligand binding domain of DSF polypeptide. 36. The method of claim 32, wherein said compound is an agonist. 37. The method of claim 32, wherein said compound is an antagonist. 38. The method of claim 30, wherein said DSF polypeptide activity is detected by expression of a reporter gene operatively linked to one or more transcriptionai regulatory elements responsive to a DSF polypeptide, said reporter gene expression providing a detection signal. 39. The method of claim 38, wherein said detection signal is selected from the group consisting of β-galactosidase, alkaline phosphatase, horseradish peroxidase, luciferase, green fluorescent protein and chloramphenicol acetyl transferase. 40. A method for isolating a protein that binds to a DSF polypeptide or functional fragment thereof, comprising: a) incubating at least one protein and a DSF polypeptide or functional fragment thereof under conditions sufficient to allow binding; b) separating bound DSF polypeptide or functional fragment thereoffrom unbound DSF polypeptide or functional fragment thereof; and c) isolating a protein that binds to the DSF polypeptide or functional fragment thereof. 41. The method of claim 40, further comprising identifying the isolated protein. 42. The method of claim 40, wherein said protein is from a library of proteins. 43. A method for identifying a protein that interacts with a DSF polypeptide or functional fragment thereof in a cell, comprising: a) obtaining a cell that expresses a DSF polypeptide or functional fragment thereof, said cell also expressing a protein suspected of interacting with said DSF polypeptide or functional fragment thereof; b) detecting an interaction between said DSF polypeptide or functional fragment thereof in said cell with an interaction partner, wherein the detection of an interaction indicates the presence of an interacting protein; c) isolating the interacting protein from the cell; and d) identifying the protein that interacts with said DSF polypeptide or functional fragment thereof. 44. A method for identifying a protein that interacts with a DSF polypeptide or functional fragment thereof in a cell, comprising: a) transforming a plurality of cells with a first nucleic acid sequence comprising a nucleic acid sequence encoding a DSF polypeptide or functional fragment thereof, said cells expressing a protein suspected of interacting with said DSF polypeptide or functional fragment thereof, said protein encoded by a second nucleic acid sequence; b) screening said cells to detect an interaction between a protein and said DSF polypeptide or functional fragment thereof, thereby identifying a cell containing a second nucleic acid sequence encoding a protein that interacts with said DSF polypeptide or functional fragment thereof; c) isolating from the identified cell the second nucleic acid sequence encoding the protein that interacts with said DSF polypeptide or functional fragment thereof; and d) sequencing the second nucleic acid sequence thereby identifying the protein that interacts with a DSF polypeptide or functional fragment thereof. 45. The method of claim 44, wherein said first nucleic acid sequence comprises a heterologous nucleic acid sequence. 46. The method of claim 45, wherein said heterologous nucleic acid sequence comprises a nucleic acid sequence encoding a chimera comprising a DSF polypeptide or functional fragment thereof and a GAL4 DNA binding domain. 47. The method of claim 44, wherein said second nucleic acid sequence comprises a heterologous nucleic acid sequence. 48. The method of claim 47, wherein said heterologous nucleic acid sequence comprises a nucleic acid sequence encoding a fusion protein comprising a polypeptide and a GAL4 activation domain. 49. The method of claim 47, wherein said heterologous nucleic acid sequence comprises a nucleic acid sequence encoding a fusion protein comprising a polypeptide and a VP16 activation domain. 50. The method of claim 44, wherein said cell is a yeast cell. 51. The method of claim 44, wherein said cell is a mammalian cell. 52. A method for identifying a nucleic acid sequence that selectively binds to a DSF polypeptide or functional fragment thereof comprising: a) contacting at least one nucleic acid sequence with a DSF polypeptide or functional fragment thereof under conditions that allow binding; b) detecting the binding of a nucleic acid sequence to a DSF polypeptide or functional fragment thereof; c) isolating the bound nucleic acid sequence; and d) identifying the nucleic acid sequence that binds to a DSF polypeptide or functional fragment thereof. 53. The method of claim 52, wherein said at least one nucleic acid sequence comprises a plurality of oligonucleotides. 54. The method of claim 52, wherein said at least one nucleic acid sequence is selected from the group consisting of: a direct repeat, inverted repeat and everted repeat sequence. 55. A nucleic acid sequence that binds a DSF polypeptide or functional fragment thereof identified by the method of claim 52.

Inventors: FINLEY KIM D, MCKEOWN MICHAEL, PITTMAN JEFF L, FINLEY, KIM, D., MCKEOWN, MICHAEL, PITTMAN, JEFF, L.
Applicants: FINLEY KIM D, MCKEOWN MICHAEL, PITTMAN JEFF L, SALK INST FOR BIOLOGICAL STUDI, FINLEY, KIM, D., MCKEOWN, MICHAEL, PITTMAN, JEFF, L., THE SALK INSTITUTE FOR BIOLOGICAL STUDIES
Application year: 1999
Main classification: C12N15
IPC codes: A01K67, C07K14