bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new role for Notch and Delta in cell fate decisions: patterning the feather array
Authors: Crowe Rebecca , Henrique Domingos , Ish-Horowicz David , Niswander Lee 
Published: April 2021

ABSTRACT
Chick embryonic feather buds arise in a distinct spatial and temporal pattern. Although many genes are implicated in the growth and differentiation of the feather buds, little is known about how the discrete pattern of the feather array is formed and which gene products may be involved. Possible candidates include Notch and its ligands, Delta and Serrate, as they play a role in numerous cell fate decisions in many organisms. Here we show that Notch-1 and Notch-2 mRNAs are expressed in the skin in a localized pattern prior to feather bud initiation. In the early stages of feather bud development, Delta-1 and Notch-1 are localized to the forming buds while Notch-2 expression is excluded from the bud. Thus, Notch and Delta-1 are expressed at the correct time and place to be players in the formation of the feather pattern. Once the initial buds form, expression of Notch and its ligands is observed within each bud. Notch-1 and -2 and Serrate-1 and -2 are expressed throughout the growth and differentiation of the feathers whereas Delta-1 transcripts are downregulated.
We have also misexpressed chick Delta-1 using a replication competent retrovirus. This results in induction of Notch-1 and-2 and a loss of feather buds from the embryo in either large or small patches. In large regions of Delta-1 misexpression, feathers are lost throughout the infected area. In contrast, in small regions of misexpression, Delta-1 expressing cells differentiate into feather buds more quickly than normal and inhibit their neighbors from accepting a feather fate. We propose a dual role for Delta-1 in promoting feather bud development and in lateral inhibition. These results implicate the Notch/Delta receptor ligand pair in the formation of the feather array.
The PASTICCINO genes of Arabidopsis thaliana are involved in the control of cell division and differentiation
Authors: Faure Jean-Denis , Vittorioso Paola , Santoni Véronique , Fraisier Vincent , Prinsen Els , Barlier Isabelle , Onckelen Harry Van , Caboche Michel , Bellini Catherine 
Published: April 2021

ABSTRACT
The control of cell division by growth regulators is critical to proper plant development. The isolation of single-gene mutants altered in the response to plant hormones should permit the identification of essential genes controlling the growth and development of plants. We have isolated mutants pasticcino belonging to 3 complementation groups (pas1, pas2, pas3) in the progeny of independent ethyl methane sulfonate and T-DNA mutagenized Arabidopsis thaliana plants. The screen was performed in the presence or absence of cytokinin. The mutants isolated were those that showed a significant hypertrophy of their apical parts when grown on cytokinin-containing medium. The pas mutants have altered embryo, leaf and root development. They display uncoordinated cell divisions which are enhanced by cytokinin. Physiological and biochemical analyses show that cytokinins are probably involved in pas phenotypes. The PAS genes have been mapped respectively to chromosomes 3, 5 and 1 and represent new plant genes involved in the control of cell division and plant development.
Mutations in the cadherin superfamily member gene dachsous cause a tissue polarity phenotype by altering frizzled signaling
Authors: Adler Paul N. , Charlton Jeannette , Liu Jingchun 
Published: April 2021

ABSTRACT
The adult cuticular wing of Drosophila is covered by an array of distally pointing hairs that reveals the planar polarity of the wing. We report here that mutations in dachsous disrupt this regular pattern, and do so by affecting frizzled signaling. dachsous encodes a large membrane protein that contains many cadherin domains and dachsous mutations cause deformed body parts. We found that mutations in dachsous also result in a tissue polarity phenotype that at the cellular level is similar to frizzled, dishevelled and prickle, as many cells form a single hair of abnormal polarity. Although their cellular phenotype is similar to frizzled, dishevelled and prickle, dachsous mutant wings display a unique and distinctive abnormal hair polarity pattern including regions of reversed polarity. The development of this pattern requires the function of frizzled pathway genes suggesting that in a dachsous mutant the frizzled pathway is functioning - but in an abnormal way. Genetic experiments indicated that dachsous was not required for the intracellular transduction of the frizzled signal. However, we found that dachsous clones disrupted the polarity of neighboring wild-type cells suggesting the possibility that dachsous affected the intercellular signaling function of frizzled. Consistent with this hypothesis we found that frizzled clones in a dachsous mutant background displayed enhanced domineering non-autonomy, and that the anatomical direction of this domineering non-autonomy was altered in regions of dachsous wings that have abnormal hair polarity. The direction of this domineering nonautonomy was coincident with the direction of the abnormal hair polarity. We conclude that dachsous causes a tissue polarity phenotype because it alters the direction of frizzled signaling.
Systematic gain-of-function genetics in Drosophila
Authors: Rørth Pernille , Szabo Kornelia , Bailey Adina , Laverty Todd , Rehm Jay , Rubin Gerald M. , Weigmann Katrin , Milán Marco , Benes Vladimir , Ansorge Wilhelm , Cohen Stephen M. 
Published: April 2021

ABSTRACT
A modular misexpression system was used to carry out systematic gain-of-function genetic screens in Drosophila. The system is based on inducible expression of genes tagged by insertion of a P-element vector carrying a GAL4-regulated promoter oriented to transcribe flanking genomic sequences. To identify genes involved in eye and wing development, the 2300 independent lines were screened for dominant phenotypes. Among many novel genes, the screen identified known genes, including hedgehog and decapentaplegic, implicated in these processes. A genetic interaction screen for suppressors of a cell migration defect in a hypomorphic slow border cells mutant identified known genes with likely roles in tyrosine kinase signaling and control of actin cytoskeleton, among many novel genes. These studies demonstrate the ability of the modular misexpression system to identify developmentally important genes and suggest that it will be generally useful for genetic interaction screens.
Apoptosis in late stage Drosophila nurse cells does not require genes within the H99 deficiency
Authors: Foley Kathleen , Cooley Lynn 
Published: April 2021

ABSTRACT
We have determined that nurse cells are cleared from the Drosophila egg chamber by apoptosis. DNA fragmentation begins in nurse cells at stage 12, following the completion of cytoplasm transfer from the nurse cells to the oocyte. During stage 13, nurse cells increasingly contain highly fragmented DNA and disappear from the egg chamber concomitantly with the formation of apoptotic vesicles containing highly fragmented nuclear material. In dumpless mutant egg chambers that fail to complete cytoplasm transport from the nurse cells, DNA fragmentation is markedly delayed and begins during stage 13, when the majority of cytoplasm is lost from the nurse cells. These data suggest the presence of cytoplasmic factors in nurse cells that inhibit the initiation of DNA fragmentation. In addition, we have examined the ovarian expression patterns of regulatory genes implicated in Drosophila apoptosis. The positive regulators, reaper (rpr), head involution defective (hid) and grim, as well as the negative regulators, DIAP1 and DIAP2, are transcribed during oogenesis. However, germline clones homozygous for the deficiency Df(3)H99, which deletes rpr, hid and grim, undergo oogenesis in a manner morphologically indistinguishable from wild type, indicating that genes within this region are not necessary for apoptosis in nurse cells.
strabismus, a novel gene that regulates tissue polarity and cell fate decisions in Drosophila
Authors: Wolff Tanya , Rubin Gerald M. 
Published: April 2021

ABSTRACT
Polarity in the Drosophila eye is manifested as a dorsoventral reflection of two chiral forms of the individual unit eyes, or ommatidia. These forms fall on opposite sides of a dorsoventral midline of mirror symmetry known as the equator. Polarity is established in the eye imaginal disc as cells adopt their fates and as the ommatidial precursors undergo coordinated rotation within the epithelium; the mechanisms that coordinate these early patterning events remain poorly understood. We have identified a novel gene, strabismus (stbm), which is required to establish polarity in the eye, legs and bristles of Drosophila. Many stbm ommatidia are reversed anteroposteriorly and/or dorsoventrally. In stbm eye discs, ommatidial rotation is delayed and some ommatidial precursors initiate rotation in the wrong direction. Mosaic analysis indicates that stbm is ommatidium autonomous and required in most, if not all, photoreceptors within an ommatidium to establish normal polarity. stbm also appears to play an instructive role during the establishment of the fates of photoreceptors R3 and R4. stbm encodes a novel protein with a potential PDZ domain-binding motif and two possible transmembrane domains. Sequence analysis of both vertebrate and invertebrate homologs indicates that stbm has been highly conserved throughout evolution.
Twist and Notch negatively regulate adult muscle differentiation in Drosophila
Authors: Anant Sumita , Roy Sudipto , VijayRaghavan K. 
Published: April 2021

ABSTRACT
Twist is required in Drosophila embryogenesis for mesodermal specification and cell-fate choice. We have examined the role of Twist and Notch during adult indirect flight muscle development. Reduction in levels of Twist leads to abnormal myogenesis. Notch reduction causes a similar mutant phenotype and reduces Twist levels. Conversely, persistent expression, in myoblasts, of activated Notch causes continued twist expression and failure of differentiation as assayed by myosin expression. The gain-of-function phenotype of Notch is very similar to that seen upon persistent twist expression. These results point to a relationship between Notch function and twist regulation during indirect flight muscle development and show that decline in Twist levels is a requirement for the differentiation of these muscles, unlike the somatic muscles of the embryo.
Independent regulation of anterior/posterior and equatorial/polar polarity in the Drosophila eye; evidence for the involvement of Wnt signaling in the equatorial/polar axis
Authors: Wehrli Marcel , Tomlinson Andrew 
Published: April 2021

ABSTRACT
The Drosophila retina is made from hundreds of asymmetric subunit ommatidia arranged in a crystalline-like array with each unit shaped and oriented in a precise way. One explanation for the precise cellular arrangements and orientations of the ommatidia is that they respond to two axes of polarized information present in the plane of the retinal epithelium. Earlier work showed that one of these axes lies in the anterior/posterior(A/P) direction and that the polarizing influence is closely associated with the sweep of the Hedgehog-dependent morphogenetic wave. Here we present evidence for a second and orthogonal axis of polarity, and show that it can be functionally separated from the A/P axis. Further, we show that the polarizing information acting in this equatorial/polar axis (Eq/Pl) is established in at least two steps – the activity of one signaling molecule functions to establish the graded activity of a second signal.
Medea is a Drosophila Smad4 homolog that is differentially required to potentiate DPP responses
Authors: Wisotzkey Robert G. , Mehra Arun , Sutherland David J. , Dobens Leonard L. , Liu Xiaoqing , Dohrmann Cord , Attisano Liliana , Raftery Laurel A. 
Published: April 2021

ABSTRACT
Mothers against dpp (Mad) mediates Decapentaplegic (DPP) signaling throughout Drosophila development. Here we demonstrate that Medea encodes a MAD-related protein that functions in DPP signaling. MEDEA is most similar to mammalian Smad4 and forms heteromeric complexes with MAD. Like dpp, Medea is essential for embryonic dorsal/ventral patterning. However, Mad is essential in the germline for oogenesis whereas Medea is dispensable. In the wing primordium, loss of Medea most severely affects regions receiving low DPP signal. MEDEA is localized in the cytoplasm, is not regulated by phosphorylation, and requires physical association with MAD for nuclear translocation. Furthermore, inactivating MEDEA mutations prevent nuclear translocation either by preventing interaction with MAD or by trapping MAD/MEDEA complexes in the cytosol. Thus MAD-mediated nuclear translocation is essential for MEDEA function. Together these data show that, while MAD is essential for mediating all DPP signals, heteromeric MAD/MEDEA complexes function to modify or enhance DPP responses. We propose that this provides a general model for Smad4/MEDEA function in signaling by the TGF-β family.
Requirement for Xvent-1 and Xvent-2 gene function in dorsoventral patterning of Xenopus mesoderm
Authors: Onichtchouk Darya , Glinka Andrei , Niehrs Christof 
Published: April 2021

ABSTRACT
Xvent-1 and Xvent-2 are members of a novel homeobox subfamily that have been implicated in dorsoventral patterning in Xenopus mesoderm and are thought to function in BMP signalling. Here we investigate the requirement for Xvent function by employing two dominant-negative strategies. Loss of Xvent function dorsalizes ventral mesoderm, induces secondary embryonic axes and directly neuralizes ectoderm. We further find that (1) Xvents act as transcriptional repressors, (2) Xvents function in an additive fashion and (3) a surprising number of genes are able to rescue dominant-negative Xvent phenotypes including Bmp-4, Smad-1 and wild-type Xvents and Xhox3, but not Xwnt-8. The results show that Xvent-1 and Xvent-2 are essential for ventral mesoderm formation and for preventing neural differentiation. A model is suggested to explain how Bmp-4 positional information is converted into distinct cellular responses.
Expression of wingless in the Drosophila embryo: a conserved cis-acting element lacking conserved Ci-binding sites is required for patched-mediated repression
Authors: Lessing Derek , Nusse Roel 
Published: April 2021

ABSTRACT
Patterning of the Drosophila embryo depends on the accurate expression of wingless (wg), which encodes a secreted signal required for segmentation and many other processes. Early expression of wg is regulated by the nuclear proteins of the gap and pair-rule gene classes but, after gastrulation, wg transcription is also dependent on cell-cell communication. Signaling to the Wg-producing cells is mediated by the secreted protein, Hedgehog (Hh), and by Cubitus interruptus (Ci), a transcriptional effector of the Hh signal transduction pathway. The transmembrane protein Patched (Ptc) acts as a negative regulator of wg expression; ptc− embryos have ectopic wg expression. According to the current models, Ptc is a receptor for Hh. The default activity of Ptc is to inhibit Ci function; when Ptc binds Hh, this inhibition is released and Ci can control wg transcription.
We have investigated cis-acting sequences that regulate wg during the time that wg expression depends on Hh signaling. We show that approximately 4.5 kb immediately upstream of the wg transcription unit can direct expression of the reporter gene lacZ in domains similar to the normal wg pattern in the embryonic ectoderm. Expression of this reporter construct expands in ptc mutants and responds to hh activity. Within this 4.5 kb, a 150 bp element, highly conserved between D. melanogaster and Drosophila virilis, is required to spatially restrict wg transcription. Activity of this element depends on ptc, but it contains no consensus Ci-binding sites. The discovery of an element that is likely to bind a transcriptional repressor was unexpected, since the prevailing model suggests that wg expression is principally controlled by Hh signaling acting through the Ci activator. We show that wg regulatory DNA can drive lacZ in a proper wg-like pattern without any conserved Ci-binding sites and suggest that Ci can not be the sole endpoint of the Hh pathway.
Sex-lethal, the master sex-determining gene in Drosophila, is not sex-specifically regulated in Musca domestica
Authors: Meise Martin , Hilfiker-Kleiner Denise , Dübendorfer Andreas , Nöthiger Claudia Brunner, Rolf , Bopp Daniel 
Published: April 2021

ABSTRACT
Sex-lethal (Sxl) is the master switch gene for somatic sex determination in Drosophila melanogaster. In XX animals, Sxl becomes activated and imposes female development; in X(Y) animals, Sxl remains inactive and male development ensues. A switch gene for sex determination, called F, has also been identified in the housefly, Musca domestica. An active F dictates female development, while male development ensues when F is inactive. To test if the switch functions of Sxl and F are founded on a common molecular basis, we isolated the homologous Sxl gene in the housefly. Though highly conserved in sequence, Musca-Sxl is not sex-specifically regulated: the same transcripts and protein isoforms are expressed in both male and female animals throughout development. Musca-Sxl is apparently not controlled by the primary sex-determining signal and, thus, is unlikely to correspond to the F gene. Ectopic expression of Musca-SXL protein in Drosophila does not exert any noticeable effects on the known target genes of endogenous Sxl. Instead, forced overexpression of the transgene eventually results in lethality of both XY and XX animals and in developmental abnormalities in some escaper XY animals. Similar results were obtained with the Sxl homologue of Ceratitis capitata (Saccone, G., Peluso, I., Artiaco, D., Giodano, E., Bopp, D. and Polito, L. C. (1998) Development 125, 1495–1500) suggesting that, in these non-drosophilid species, Sxl performs a function different from that in sex determination.
The Ceratitis capitata homologue of the Drosophila sex-determining gene Sex-lethal is structurally conserved, but not sex-specifically regulated
Authors: Saccone Giuseppe , Peluso Ivana , Artiaco Dora , Giordano Ennio , Bopp Daniel , Polito Lino C. 
Published: April 2021

ABSTRACT
In Drosophila, Sxl functions as a binary switch in sex determination. Under the control of the primary sex-determining signal, it produces functional protein only in XX animals to implement female development. Here we report that, in contrast to Drosophila, the Sxl homologue in the Medfly, Ceratitis capitata, expresses the same mRNAs and protein isoforms in both XX and XY animals irrespective of the primary sex-determining signal. Also, experiments with two inducible transgenes demonstrate that the corresponding Ceratitis SXL product has no significant sex-transforming effects when expressed in Drosophila. Similar results have been obtained for the Sxl homologue of Musca domestica (Meise, M., Hilfiker-Kleiner, D., Brunner, C., Dübendorfer, A., Nöthiger, R. and Bopp, D. (1998) Development 125, 1487-1494). Our findings suggest that Sxl acquired its master regulatory role in sex determination during evolution of the Acalyptratae group, most probably after phylogenetic divergence of the genus Drosophila from other genera of this group.
The FRUITFULL MADS-box gene mediates cell differentiation during Arabidopsis fruit development
Authors: Gu Qing , Ferrándiz Cristina , Yanofsky Martin F. , Martienssen Robert 
Published: April 2021

ABSTRACT
Fruit morphogenesis is a process unique to flowering plants, and yet little is known about its developmental control. Following fertilization, fruits typically undergo a dramatic enlargement that is accompanied by differentiation of numerous distinct cell types. We have identified a mutation in Arabidopsis called fruitfull (ful-1), which abolishes elongation of the silique after fertilization. The ful-1 mutation is caused by the insertion of a DsE transposable enhancer trap element into the 5′ untranslated leader of the AGL8 MADS-box gene. β-glucuronidase (GUS) reporter gene expression in the enhancer trap line is observed specifically in all cell layers of the valve tissue, but not in the replum, the septum or the seeds, and faithfully mimics RNA in situ hybridization data reported previously. The lack of coordinated growth of the fruit tissues leads to crowded seeds, a failure of dehiscence and, frequently, the premature rupture of the carpel valves. The primary defect of ful-1 fruits is within the valves, whose cells fail to elongate and differentiate. Stomata, which are frequent along the epidermis of wild-type valves, are completely eliminated in the ful mutant valves. In addition to the effect on fruit development, ful cauline leaves are broader than those of wild type and show a reduction in the number of internal cell layers. These data suggest that AGL8/FUL regulates the transcription of genes required for cellular differentiation during fruit and leaf development.
Mouse mutant embryos lacking huntingtin are rescued from lethality by wild-type extraembryonic tissues
Authors: Dragatsis Ioannis , Efstratiadis Argiris , Zeitlin Scott 
Published: April 2021

ABSTRACT
Mouse embryos nullizygous for a targeted disruption of the Huntington’s disease gene homologue (Hdh), which encodes a protein (huntingtin) of unknown biochemical function, become developmentally retarded and disorganized, and die early in development. Using chimeric analysis, we demonstrate that extensively chimeric embryos derived by injection of Hdh null ES cells into wild-type host blastocysts are rescued from lethality. In contrast, when wild-type ES cells are injected into Hdh null blastocysts, the chimeric embryos are morphologically indistinguishable from Hdh null mutants derived from natural matings, and die shortly after gastrulation. Therefore, the primary defect in the absence of huntingtin lies in extraembryonic tissues, whereas the epiblast and its derivatives are affected secondarily. It is likely that the mutation results in impairment of the nutritive functions of the visceral endoderm, which otherwise appears to differentiate normally, as evidenced by the expression of several specific marker genes. Consistent with preliminary histochemical analysis indicating that at least the transport of ferric ions is defective in Hdh mutants and in conjunction with the known localization of huntingtin in the membranes of vesicles associated with microtubules, we hypothesize that this protein is involved in the intracellular trafficking of nutrients in early embryos.