BACKGROUND
tgfβ pathways are conserved between primitive animals, such as sponges and sea anemone  <cit>  and vertebrates, thus representing an ancient signal transduction pathway.
in both vertebrates and invertebrates, tgfβ family members play fundamental roles in proliferation, pattern formation, apoptosis, and specification of cell fate.
mutations of various tgfβ signaling components are associated with human diseases including cancer  <cit> .
in recent years, the core signaling components of the tgfβ pathways have been elucidated by a combination of genetics and biochemical approaches.
unique to these signaling pathways are transmembrane receptor serine-threonine kinases that are novel in animals.
signaling is initiated when dimeric ligands bind to the type i receptor or a complex of the type i and type ii receptors.
the type ii receptor phosphorylates the type i receptor, which renders it active.
r-smads are phosphorylated by the type i receptor, the complex with a co-smad, and translocate to the nucleus.
smads bind dna promoter elements weakly and require co-factors for efficient regulation of target genes.
in drosophila, seven ligands have been identified from the genomic sequence  <cit> .
these ligands act through a receptor complex comprised of heterodimeric combinations of type i and type ii receptors.
three type i receptors, thick veins , saxophone, baboon  and two type ii receptors, punt and wishful thinking , interact with either of two r-smads, mothers against dpp  or dsmad <dig>  <cit> .
although different heteromeric combinations of receptors exist, in general, tkv transmits a dpp/bmp signal through mad, and babo transmits an activin signal through dsmad <dig>
the dpp and activin pathways have known functions in the brain, although our understanding of it role is rudimentary.
dpp is expressed in two areas adjacent to the outer proliferation center , where it modulates wingless expression  <cit> .
to acquire the adult pattern of projections, extensive remodeling occurs in neurons of the larval neural circuits during metamorphosis  <cit> .
proper neuronal remodeling is important for transformation of the larval mushroom bodies  to the adult mbs  <cit> .
babo and dsmad <dig>  are involved in neuronal remodeling, which occurs in the larval-pupal transition  <cit> .
one target of the activin pathway identified in these studies is a subunit of the ecdysone receptor, ecr-b.
neuronal remodeling is essential for brain development in most animals and this result raises the question of possible conservation of neuronal targets in vertebrates.
in spite of intense study using classical genetic approaches and biochemical methods, very few targets of the pathway have been identified.
a better understanding of the growth and patterning properties of the pathway require a more complete list of target genes.
using activated receptors , we have used microarray technology to identify common targets of the bmp and activin pathways in the drosophila brain.
RESULTS
identifying targets of babo and tkv in drosophila brains
few targets of tkv signaling and even fewer targets of babo signaling are known in drosophila.
though multiple ligands and type ii receptors may interact with these type i receptors, the use of ligand/receptor combinations is not yet established with certainty.
however, in a simplified view, tkv and babo send dpp  and activin signals.
these pathways and receptors are conserved through evolution, but few downstream targets are known for these pathways in any organism.
to learn more about the growth regulatory and pattering properties of these signals in the fly brain, we used microarray technology to identify downstream targets.
in these experiments, affymetrix™ chips containing the entire protein coding capacity of the drosophila genome  were screened.
genomic-wide microarray analysis allows us to examine similarities and differences between two signaling pathways in a tissue where both are known to function.
constitutively active forms of the receptors were made by single amino acid substitutions  <cit> , rendering them active in the absence of ligand.
transformants were generated which could be transcriptionally expressed using the heat shock gal <dig> driver   <cit> .
to assay for the best induction protocol, animals were heat shocked and monitored for the presence of a uas-gfp reporter.
since additional time is required for the induction of downstream signaling targets versus the time required for appearance of the gfp reporter, we collected rna samples from third instar larvae in a broad time period roughly  <dig> minutes after the peak of gfp expression.
data resulting from induced ectopic expression of tkv, and babo were compared with each other and to the control .
three independent replicates for each treatment were generated.
hierarchical clustering  and principal component analysis  indicated that the microarray data is highly reproducible.
only transcripts that show an expression level above  <dig>  fold change at significance values of p <  <dig>   were considered to be differentially expressed.
these experiments identified genes that are either regulated by both tkv and babo pathways or by one of the pathways only.
to verify the differential expression levels in response to ectopic expression of tkv and babo on microarrays, semi-quantitative real-time rt-pcr was performed on selected genes.
six among the  <dig> genes were picked for validation.
real time rt-pcr showed similar results similar to the microarray results for four of the six genes .
these pcr results are consistent with those of other reported microarray experiments  <cit> .
this data, with the reproducibility of the individual samples analyzed, establish the validity of our microarray data and provide a comparison of two signaling pathways in the drosophila brain.
overview of gene expression following ectopic expression of babo and tkv
upon ectopic expression of tkv,  <dig> transcripts are detected with differential expression values in brain tissues when compared with the control .
this corresponds to about  <dig> % of the transcripts on the array.
more transcripts are down regulated  than up regulated  in abundance levels, indicating that ectopic expression of tkv causes both repression and activation of downstream genes.
induction of activated babo results in  <dig> genes with differential expression values in brain tissues.
interestingly, expression levels of more transcripts are decreased  than increased  .
this corresponds to about  <dig> % of the transcripts on the array.
most importantly, there are  <dig> genes co-regulated by induction of both babo and tkv –  <dig> of these transcripts are down regulated and  <dig> of them are up regulated .
role for tgfβ signaling in neuronal remodeling
the fact that both dpp and activin signaling pathways share some common features in differentiation and growth control in various tissues suggests that both pathways might share some downstream target genes.
microarray experiments identified  <dig> genes  co-regulated by the induced expression of both tkv and babo.
among these  <dig> co-regulated transcripts, there are transcription factors, enzymes, transporters, signal transducers, miscellaneous proteins and four unknown genes .
the transcription factor ultraspiracle  gene has the highest expression level increase , which is a subunit of a nuclear receptor  <cit> .
usp forms a heterodimer with the nuclear ecdysone receptor  and participates in neuronal remodeling  <cit> .
previous studies have shown that the drosophila activin signaling pathway partially mediates neuronal remodeling through regulating ecr-b <dig> expression  <cit> .
two independent mutations that block neuronal remodeling in the mushroom bodies  during pupation were found to reside in babo and dsmad <dig>  <cit> , both of which have been shown to participate in the activin signaling pathway  <cit> .
further, mutations in these signaling components reduce the expression of ecr-b <dig>  and restoration of ecr-b <dig> expression rescues neuronal remodeling defects.
these observations led to the model that the drosophila activin signaling results in induction of the ecr-b <dig> isoform.
upon binding of ecdysone to the ecr-b1/usp heterodimeric receptors, neuronal remodeling is initiated via transcriptional activation of downstream target genes  <cit> .
our microarray analysis shows that high level expression of usp is also induced by ectopic expression of tkv and babo.
in addition, we find that ecr-a expression is repressed by the induction of babo.
using real-time pcr, we confirmed that ecr-b <dig> is induced by ectopic expression of babo , a more modest change than the increases on usp by tkv and babo.
these finding suggest that drosophila activin signaling mediates neuronal remodeling by regulation of both ecr-b <dig> and usp expression, while inhibiting ecr-a induction.
bmp-like pathways, as well as activin pathways, have been implicated in neuronal remodeling  <cit> .
punt and wit have been shown to have a redundant function in inducing ecr-b <dig> expression during brain development.
in mutant clones, levels of ecr-b <dig> were unaffected, unless both receptors were mutant.
these results are consistent with our findings that activated tkv and babo both induce ecr-b <dig>  although it is not known which receptor combinations or ligands are responsible for these effects.
dpp  has other known roles in organizing the visual center of the brain  <cit> .
it has been shown that wingless, acting through dpp, is an important participant in organizing the optical centers of the brain  <cit> .
wingless is expressed at the tips of the crescent shaped opc.
fourteen hours later, wingless induces dpp expression in adjacent cells, in two spots in each brain hemisphere.
these dpp expressing cells also express fasciclin ii.
brdu staining shows that wingless, dpp, and fasciclin ii expressing cells proliferate throughout larval development.
however, a reduction of wingless or dpp results in a reduction in the rate of proliferation in the opc, resulting in smaller optic lobes of the brain.
loss of wingless also results in a severe reduction of the medulla, where the photoreceptor axons r <dig> and r <dig> migrate.
another defect noted in wingless mutant animals is that the opc derived precursor cells had failed to assume their proper neuronal fate.
transcription factors regulated by both dpp and activin pathways
besides usp, two other transcription factor genes, cg <dig> and tfiifβ, are up regulated by tkv and babo.
both are implicated in growth processes.
cg <dig> has 30% homology over  <dig> residues to c. elegans f23b <dig> , which shows a slow growing phenotype in rnai experiments  <cit> .
tfiifβ is part of the rna transcriptional machinery, and 28% of glioblastomas and 80% of astrocytomas show amplification of this gene.
perhaps part of the growth potential of the tkv and babo tgfβ pathways operate through these transcription factors.
two transcription factors, cg <dig> and antennapedia , are down regulated by both pathways during brain development.
antp is a well-studied hox gene in drosophila, which controls many developmental decisions, most notably, the differentiation of the antennae and legs from homologous structures  <cit> .
the enormous diversity of body plans in animals is partially due to the variations that hox transcription factors regulate gene expression.
most animals have one or more clusters of hox genes, and each hox gene controls the development of a specific region of the body plan  <cit> .
in drosophila, differences between segments, such as the presence or absence of appendages, are often controlled by hox transcription factors.
the role of antp in brain development is not known, but it is tempting to speculate that both dpp and activin might regulate brain development, at least partially, through interaction with the hox gene antp.
determining the mechanisms by which hox proteins regulate gene expression will be important for understanding animal development and pattern formation.
other genes regulated by tkv and babo pathways
many of the other genes that are significantly regulated by tkv and babo are evolutionarily conserved throughout animal phyla.
quantitative analysis of transcript levels indicates that tgfβ controls some genes that encode kinases and phosphatases that might be involved in signaling pathways.
for example, ia <dig>  a transmembrane receptor protein phosphatase  <cit> , has the highest level of transcriptional change among these kinases and phosphatases.
antibodies to the human version of the gene are often indicative of diabetes  <cit> .
ninac is a protein serine/threonine kinase  <cit>  with calmodulin binding activity  <cit> .
cg <dig> is a calcium-dependent protein serine-threonine phosphatase, which is down regulated.
it is strongly related to c. elegans f30a <dig> , which is involved in negative regulation of body size.
if the function of the protein has also been conserved, then down-regulation by the tgfβ-like pathways would allow growth in the developing brain.
other kinases and phosphatases co-regulated by both tgfβ pathways are g-iα65a , a g-protein coupled receptor protein involved in neuroblast cell division and cell size control  <cit> , and cg  <dig>  a calcium-dependent protein serine/threonine phosphatase  <cit> .
cg <dig> and cg <dig> are two novel proteins that have homologs in c. elegans and in vertebrates.
while their molecular functions are not currently known, the c. elegans cg <dig> homolog f41e <dig>  is involved in positive regulation of growth.
rnai experiments with the c. elegans homolog of cg <dig>  y54e2a.
<dig>  revealed no mutant phenotype.
four transporters  are transporters regulated by the tkv and babo pathways.
fatp is a long-chain fatty acid transporter.
atpa is a sodium/potassium-exchanging atpase, while cg <dig> is a glutamate-gated ion channel and cg <dig> is a l-ascorbate:sodium symporter.
CONCLUSIONS
microarray experiments revealed that  <dig> genes are co-regulated in both tkv and babo signaling pathways in the developing drosophila brain.
one of the most striking developmental events in the fly brain is neuronal remodeling.
these results indicate usp is positively regulated by tkv and babo, and thus adds another important link to their roles in brain remodeling.
many of the  <dig> genes are strongly conserved in other species.
if their biological functions are also conserved, then the rnai experiments in their c. elegans counterparts show that several of them are involved in growth regulation.
this is particularly useful since few downstream targets of bmp or activin signaling pathways are known, particularly the targets that execute their growth regulatory properties.
not surprisingly, mutational analysis of several of these genes has not been done, but the genetic tools in drosophila make this relatively straightforward.
further characterization of these downstream genes may provide insights into the integration of tkv and babo signaling pathways in drosophila brain development, and provide hints into their functions in other organisms.

 tgfβ pathways are conserved between primitive animals, such as sponges and sea anemone and vertebrates, thus representing an ancient signal transduction pathway. in both vertebrates and invertebrates, tgfβ family members play fundamental roles in proliferation, pattern formation, apoptosis, and specification of cell fate. mutations of various tgfβ signaling components are associated with human diseases including cancer. in recent years, the core signaling components of the tgfβ pathways have been elucidated by a combination of genetics and biochemical approaches. unique to these signaling pathways are transmembrane receptor serine-threonine kinases that are novel in animals. signaling is initiated when dimeric ligands bind to the type i receptor or a complex of the type i and type ii receptors. the type ii receptor phosphorylates the type i receptor, which renders it active. r-smads are phosphorylated by the type i receptor, the complex with a co-smad, and translocate to the nucleus. smads bind dna promoter elements weakly and require co-factors for efficient regulation of target genes. in drosophila, seven ligands have been identified from the genomic sequence. these ligands act through a receptor complex comprised of heterodimeric combinations of type i and type ii receptors. three type i receptors, thick veins, saxophone, baboon and two type ii receptors, punt and wishful thinking, interact with either of two r-smads, mothers against dpp or dsmad. although different heteromeric combinations of receptors exist, in general, tkv transmits a dpp/bmp signal through mad, and babo transmits an activin signal through dsmad the dpp and activin pathways have known functions in the brain, although our understanding of it role is rudimentary. dpp is expressed in two areas adjacent to the outer proliferation center, where it modulates wingless expression. to acquire the adult pattern of projections, extensive remodeling occurs in neurons of the larval neural circuits during metamorphosis. proper neuronal remodeling is important for transformation of the larval mushroom bodies to the adult mbs. babo and dsmad are involved in neuronal remodeling, which occurs in the larval-pupal transition. one target of the activin pathway identified in these studies is a subunit of the ecdysone receptor, ecr-b. neuronal remodeling is essential for brain development in most animals and this result raises the question of possible conservation of neuronal targets in vertebrates. in spite of intense study using classical genetic approaches and biochemical methods, very few targets of the pathway have been identified. a better understanding of the growth and patterning properties of the pathway require a more complete list of target genes. using activated receptors, we have used microarray technology to identify common targets of the bmp and activin pathways in the drosophila brain.  identifying targets of babo and tkv in drosophila brains few targets of tkv signaling and even fewer targets of babo signaling are known in drosophila. though multiple ligands and type ii receptors may interact with these type i receptors, the use of ligand/receptor combinations is not yet established with certainty. however, in a simplified view, tkv and babo send dpp and activin signals. these pathways and receptors are conserved through evolution, but few downstream targets are known for these pathways in any organism. to learn more about the growth regulatory and pattering properties of these signals in the fly brain, we used microarray technology to identify downstream targets. in these experiments, affymetrix™ chips containing the entire protein coding capacity of the drosophila genome were screened. genomic-wide microarray analysis allows us to examine similarities and differences between two signaling pathways in a tissue where both are known to function. constitutively active forms of the receptors were made by single amino acid substitutions, rendering them active in the absence of ligand. transformants were generated which could be transcriptionally expressed using the heat shock gal driver. to assay for the best induction protocol, animals were heat shocked and monitored for the presence of a uas-gfp reporter. since additional time is required for the induction of downstream signaling targets versus the time required for appearance of the gfp reporter, we collected rna samples from third instar larvae in a broad time period roughly minutes after the peak of gfp expression. data resulting from induced ectopic expression of tkv, and babo were compared with each other and to the control. three independent replicates for each treatment were generated. hierarchical clustering and principal component analysis indicated that the microarray data is highly reproducible. only transcripts that show an expression level above fold change at significance values of p < were considered to be differentially expressed. these experiments identified genes that are either regulated by both tkv and babo pathways or by one of the pathways only. to verify the differential expression levels in response to ectopic expression of tkv and babo on microarrays, semi-quantitative real-time rt-pcr was performed on selected genes. six among the genes were picked for validation. real time rt-pcr showed similar results similar to the microarray results for four of the six genes. these pcr results are consistent with those of other reported microarray experiments. this data, with the reproducibility of the individual samples analyzed, establish the validity of our microarray data and provide a comparison of two signaling pathways in the drosophila brain. overview of gene expression following ectopic expression of babo and tkv upon ectopic expression of tkv, transcripts are detected with differential expression values in brain tissues when compared with the control. this corresponds to about % of the transcripts on the array. more transcripts are down regulated than up regulated in abundance levels, indicating that ectopic expression of tkv causes both repression and activation of downstream genes. induction of activated babo results in genes with differential expression values in brain tissues. interestingly, expression levels of more transcripts are decreased than increased. this corresponds to about % of the transcripts on the array. most importantly, there are genes co-regulated by induction of both babo and tkv – of these transcripts are down regulated and of them are up regulated. role for tgfβ signaling in neuronal remodeling the fact that both dpp and activin signaling pathways share some common features in differentiation and growth control in various tissues suggests that both pathways might share some downstream target genes. microarray experiments identified genes co-regulated by the induced expression of both tkv and babo. among these co-regulated transcripts, there are transcription factors, enzymes, transporters, signal transducers, miscellaneous proteins and four unknown genes. the transcription factor ultraspiracle gene has the highest expression level increase, which is a subunit of a nuclear receptor. usp forms a heterodimer with the nuclear ecdysone receptor and participates in neuronal remodeling. previous studies have shown that the drosophila activin signaling pathway partially mediates neuronal remodeling through regulating ecr-b expression. two independent mutations that block neuronal remodeling in the mushroom bodies during pupation were found to reside in babo and dsmad, both of which have been shown to participate in the activin signaling pathway. further, mutations in these signaling components reduce the expression of ecr-b and restoration of ecr-b expression rescues neuronal remodeling defects. these observations led to the model that the drosophila activin signaling results in induction of the ecr-b isoform. upon binding of ecdysone to the ecr-b1/usp heterodimeric receptors, neuronal remodeling is initiated via transcriptional activation of downstream target genes. our microarray analysis shows that high level expression of usp is also induced by ectopic expression of tkv and babo. in addition, we find that ecr-a expression is repressed by the induction of babo. using real-time pcr, we confirmed that ecr-b is induced by ectopic expression of babo, a more modest change than the increases on usp by tkv and babo. these finding suggest that drosophila activin signaling mediates neuronal remodeling by regulation of both ecr-b and usp expression, while inhibiting ecr-a induction. bmp-like pathways, as well as activin pathways, have been implicated in neuronal remodeling. punt and wit have been shown to have a redundant function in inducing ecr-b expression during brain development. in mutant clones, levels of ecr-b were unaffected, unless both receptors were mutant. these results are consistent with our findings that activated tkv and babo both induce ecr-b although it is not known which receptor combinations or ligands are responsible for these effects. dpp has other known roles in organizing the visual center of the brain. it has been shown that wingless, acting through dpp, is an important participant in organizing the optical centers of the brain. wingless is expressed at the tips of the crescent shaped opc. fourteen hours later, wingless induces dpp expression in adjacent cells, in two spots in each brain hemisphere. these dpp expressing cells also express fasciclin ii. brdu staining shows that wingless, dpp, and fasciclin ii expressing cells proliferate throughout larval development. however, a reduction of wingless or dpp results in a reduction in the rate of proliferation in the opc, resulting in smaller optic lobes of the brain. loss of wingless also results in a severe reduction of the medulla, where the photoreceptor axons r and r migrate. another defect noted in wingless mutant animals is that the opc derived precursor cells had failed to assume their proper neuronal fate. transcription factors regulated by both dpp and activin pathways besides usp, two other transcription factor genes, cg and tfiifβ, are up regulated by tkv and babo. both are implicated in growth processes. cg has 30% homology over residues to c. elegans f23b, which shows a slow growing phenotype in rnai experiments. tfiifβ is part of the rna transcriptional machinery, and 28% of glioblastomas and 80% of astrocytomas show amplification of this gene. perhaps part of the growth potential of the tkv and babo tgfβ pathways operate through these transcription factors. two transcription factors, cg and antennapedia, are down regulated by both pathways during brain development. antp is a well-studied hox gene in drosophila, which controls many developmental decisions, most notably, the differentiation of the antennae and legs from homologous structures. the enormous diversity of body plans in animals is partially due to the variations that hox transcription factors regulate gene expression. most animals have one or more clusters of hox genes, and each hox gene controls the development of a specific region of the body plan. in drosophila, differences between segments, such as the presence or absence of appendages, are often controlled by hox transcription factors. the role of antp in brain development is not known, but it is tempting to speculate that both dpp and activin might regulate brain development, at least partially, through interaction with the hox gene antp. determining the mechanisms by which hox proteins regulate gene expression will be important for understanding animal development and pattern formation. other genes regulated by tkv and babo pathways many of the other genes that are significantly regulated by tkv and babo are evolutionarily conserved throughout animal phyla. quantitative analysis of transcript levels indicates that tgfβ controls some genes that encode kinases and phosphatases that might be involved in signaling pathways. for example, ia a transmembrane receptor protein phosphatase, has the highest level of transcriptional change among these kinases and phosphatases. antibodies to the human version of the gene are often indicative of diabetes. ninac is a protein serine/threonine kinase with calmodulin binding activity. cg is a calcium-dependent protein serine-threonine phosphatase, which is down regulated. it is strongly related to c. elegans f30a, which is involved in negative regulation of body size. if the function of the protein has also been conserved, then down-regulation by the tgfβ-like pathways would allow growth in the developing brain. other kinases and phosphatases co-regulated by both tgfβ pathways are g-iα65a, a g-protein coupled receptor protein involved in neuroblast cell division and cell size control, and cg a calcium-dependent protein serine/threonine phosphatase. cg and cg are two novel proteins that have homologs in c. elegans and in vertebrates. while their molecular functions are not currently known, the c. elegans cg homolog f41e is involved in positive regulation of growth. rnai experiments with the c. elegans homolog of cg y54e2a. revealed no mutant phenotype. four transporters are transporters regulated by the tkv and babo pathways. fatp is a long-chain fatty acid transporter. atpa is a sodium/potassium-exchanging atpase, while cg is a glutamate-gated ion channel and cg is a l-ascorbate:sodium symporter.  microarray experiments revealed that genes are co-regulated in both tkv and babo signaling pathways in the developing drosophila brain. one of the most striking developmental events in the fly brain is neuronal remodeling. these results indicate usp is positively regulated by tkv and babo, and thus adds another important link to their roles in brain remodeling. many of the genes are strongly conserved in other species. if their biological functions are also conserved, then the rnai experiments in their c. elegans counterparts show that several of them are involved in growth regulation. this is particularly useful since few downstream targets of bmp or activin signaling pathways are known, particularly the targets that execute their growth regulatory properties. not surprisingly, mutational analysis of several of these genes has not been done, but the genetic tools in drosophila make this relatively straightforward. further characterization of these downstream genes may provide insights into the integration of tkv and babo signaling pathways in drosophila brain development, and provide hints into their functions in other organisms. 
in drosophila, there are seven ligands that function through combinations of three type i receptors and two type ii receptors. these signals can be roughly grouped into two major tgfβ pathways, the dpp/bmp and activin pathways, which signal primarily through thick veins and baboon. in these experiments, we compare the similarities of target genes of these two pathways in the brain. many of these genes are novel and several genes are implicated in growth control. these regulated genes cluster into various functional groups such as dna/rna binding, signal transducers, enzymes, transcription regulators, and neuronal regulators. few downstream targets are known for either pathway, especially targets expressed in the drosophila brain. our genomic-wide microarray analysis has revealed common targets for the tkv and babo pathways and provided new insights into downstream effectors of two distinct tgfβ like pathways. we have identified targets for the tkv and babo pathways by employing microarray techniques using activated forms of the receptors expressed in the brain. twenty-seven genes are co-regulated fold by both the tkv and babo pathways.
 members of tgfβ superfamily are found to play important roles in many cellular processes, such as proliferation, differentiation, development, apoptosis, and cancer. in drosophila, there are seven ligands that function through combinations of three type i receptors and two type ii receptors. these signals can be roughly grouped into two major tgfβ pathways, the dpp/bmp and activin pathways, which signal primarily through thick veins and baboon. few downstream targets are known for either pathway, especially targets expressed in the drosophila brain.  tkv and babo both affect the growth of tissues, but have varying effects on patterning. we have identified targets for the tkv and babo pathways by employing microarray techniques using activated forms of the receptors expressed in the brain. in these experiments, we compare the similarities of target genes of these two pathways in the brain. about of examined genes changed expression at 95% confidence level. twenty-seven genes are co-regulated fold by both the tkv and babo pathways. these regulated genes cluster into various functional groups such as dna/rna binding, signal transducers, enzymes, transcription regulators, and neuronal regulators. rnai knockdown experiments of homologs of several of these genes show abnormal growth regulation, suggesting these genes may execute the growth properties of tgfβ.  our genomic-wide microarray analysis has revealed common targets for the tkv and babo pathways and provided new insights into downstream effectors of two distinct tgfβ like pathways. many of these genes are novel and several genes are implicated in growth control. among the genes regulated by both pathways is ultraspiracle, which further connects tgfβ with neuronal remodeling. 