Regulation of broad by the Notch pathway affects timing of follicle cell development.

During Drosophila oogenesis, activation of Notch signaling in the follicular epithelium (FE) around stage 6 of oogenesis is essential for entry into the endocycle and a series of other changes such as cell differentiation and migration of subsets of the follicle cells. Notch induces the expression of zinc finger protein Hindsight and suppresses homeodomain protein Cut to regulate the mitotic/endocycle (ME) switch. Here we report that broad (br), encoding a small group of zinc-finger transcription factors resulting from alternative splicing, is a transcriptional target of Notch nuclear effector Suppressor of Hairless (Su(H)). The early pattern of Br in the FE, uniformly expressed except in the polar cells, is established by Notch signaling around stage 6, through the binding of Su(H) to the br early enhancer (brE) region. Mutation of the Su(H) binding site leads to a significant reduction of brE reporter expression in follicle cells undergoing the endocycle. Chromatin immunoprecipitation results further confirm Su(H) binding to the br early enhancer. Consistent with its expression in follicle cells during midoogenesis, loss of br function results in a delayed entry into the endocycle. Our findings suggest an important role of br in the timing of follicle cell development, and its transcriptional regulation by the Notch pathway.

[1]  S. Lindquist,et al.  The FLP recombinase of yeast catalyzes site-specific recombination in the drosophila genome , 1989, Cell.

[2]  D. Johnston,et al.  Polarization of both major body axes in Drosophila by gurken-torpedo signalling , 1995, Nature.

[3]  G. E. Carney,et al.  Ecdysone receptor expression and activity in adult Drosophila melanogaster. , 2011, Journal of insect physiology.

[4]  Mark Rebeiz,et al.  SCORE: A computational approach to the identification of cis-regulatory modules and target genes in whole-genome sequence data , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  C. Berg,et al.  Juxtaposition between two cell types is necessary for dorsal appendage tube formation , 2005, Mechanisms of Development.

[6]  Rickard Sandberg,et al.  Notch signaling: simplicity in design, versatility in function , 2011, Development.

[7]  W. Deng,et al.  Cell-cell communication and axis specification in the Drosophila oocyte. , 2007, Developmental biology.

[8]  Boris Adryan,et al.  Specificity of Notch pathway activation: Twist controls the transcriptional output in adult muscle progenitors , 2010, Development.

[9]  L. Riddiford,et al.  Border of Notch activity establishes a boundary between the two dorsal appendage tube cell types. , 2006, Developmental biology.

[10]  Wu-Min Deng,et al.  Hindsight mediates the role of notch in suppressing hedgehog signaling and cell proliferation. , 2007, Developmental cell.

[11]  M. Bownes,et al.  The function of the broad-complex during Drosophila melanogaster oogenesis. , 1999, Genetics.

[12]  T. Schüpbach,et al.  The drosophila dorsoventral patterning gene gurken produces a dorsally localized RNA and encodes a TGFα-like protein , 1993, Cell.

[13]  S. Zipursky,et al.  Induction of Drosophila eye development by decapentaplegic. , 1997, Development.

[14]  D. Withers,et al.  The Drosophila Broad-Complex encodes a family of related proteins containing zinc fingers. , 1991, Genetics.

[15]  S. Barolo,et al.  A Notch-Independent Activity of Suppressor of Hairless Is Required for Normal Mechanoreceptor Physiology , 2000, Cell.

[16]  Lily S. Cheung,et al.  Transcriptional interpretation of the EGF receptor signaling gradient , 2012, Proceedings of the National Academy of Sciences.

[17]  Wu-Min Deng,et al.  At the crossroads of differentiation and proliferation: Precise control of cell‐cycle changes by multiple signaling pathways in Drosophila follicle cells , 2011, BioEssays : news and reviews in molecular, cellular and developmental biology.

[18]  M. Muskavitch,et al.  Complex function and expression of Delta during Drosophila oogenesis. , 1993, Genetics.

[19]  D. St Johnston,et al.  Drosophila nicastrin is essential for the intramembranous cleavage of notch. , 2002, Developmental cell.

[20]  Y. Jan,et al.  Role of neurogenic genes in establishment of follicle cell fate and oocyte polarity during oogenesis in Drosophila , 1991, Cell.

[21]  G. Rubin,et al.  Analysis of genetic mosaics in developing and adult Drosophila tissues. , 1993, Development.

[22]  G. Struhl,et al.  Nicastrin is required for Presenilin-mediated transmembrane cleavage in Drosophila , 2001, Nature Cell Biology.

[23]  W. Deng,et al.  The Hippo Pathway Promotes Notch Signaling in Regulation of Cell Differentiation, Proliferation, and Oocyte Polarity , 2008, PloS one.

[24]  Xiaofeng Zhou,et al.  Broad specifies pupal development and mediates the 'status quo' action of juvenile hormone on the pupal-adult transformation in Drosophila and Manduca. , 2002, Development.

[25]  J. Posakony,et al.  Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity. , 1995, Genes & development.

[26]  W. Deng,et al.  Dystroglycan down-regulation links EGF receptor signaling and anterior–posterior polarity formation in the Drosophila oocyte , 2006, Proceedings of the National Academy of Sciences.

[27]  Justin Crocker,et al.  Dynamic evolution of precise regulatory encodings creates the clustered site signature of enhancers , 2010, Nature communications.

[28]  M. Bownes,et al.  Two signalling pathways specify localised expression of the Broad-Complex in Drosophila eggshell patterning and morphogenesis. , 1997, Development.

[29]  S. Ho,et al.  Site-directed mutagenesis by overlap extension using the polymerase chain reaction. , 1989, Gene.

[30]  D. St Johnston,et al.  Patterning of the follicle cell epithelium along the anterior-posterior axis during Drosophila oogenesis. , 1998, Development.

[31]  B. Housden,et al.  A Correction to the Research Article Titled "Direct Response to Notch Activation: Signaling Crosstalk and Incoherent Logic" by A. Krejčí, F. Bernard, B. Housden, S. Collins, S. J. Bray , 2009, Science Signaling.

[32]  T. Schüpbach,et al.  cornichon and the EGF receptor signaling process are necessary for both anterior-posterior and dorsal-ventral pattern formation in Drosophila , 1995, Cell.

[33]  T. Schüpbach,et al.  CoREST acts as a positive regulator of Notch signaling in the follicle cells of Drosophila melanogaster , 2012, Journal of Cell Science.

[34]  I. Kiss,et al.  Cytogenetic analysis of the 2B3-4-2B11 Region of the X-chromosome of Drosophila melanogaster , 2004, Chromosoma.

[35]  H. Johnston,et al.  Delta signaling from the germ line controls the proliferation and differentiation of the somatic follicle cells during Drosophila oogenesis , 2001 .

[36]  J. Fristrom,et al.  Three neighboring genes interact with the Broad-Complex and the Stubble-stubbloid locus to affect imaginal disc morphogenesis in Drosophila. , 1991, Genetics.

[37]  A. Spradling,et al.  Cell cycle control of chorion gene amplification. , 1998, Genes & development.

[38]  H. Ruohola-Baker,et al.  Notch-Delta signaling induces a transition from mitotic cell cycle to endocycle in Drosophila follicle cells. , 2001, Development.

[39]  W. Deng,et al.  The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila development , 2011, Biology Open.

[40]  Fabrice Carballès,et al.  The Drosophila cytokine receptor Domeless controls border cell migration and epithelial polarization during oogenesis , 2002, Development.

[41]  Jingxia Xu,et al.  Notch Signaling during Oogenesis in Drosophila melanogaster , 2012, Genetics research international.

[42]  Liqun Luo,et al.  Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development , 2001, Trends in Neurosciences.

[43]  D. Montell,et al.  Spatially localized Kuzbanian required for specific activation of Notch during border cell migration. , 2007, Developmental biology.

[44]  Wu-Min Deng,et al.  Notch-dependent downregulation of the homeodomain gene cut is required for the mitotic cycle/endocycle switch and cell differentiation in Drosophila follicle cells , 2005, Development.

[45]  Gary D. Stormo,et al.  Identifying DNA and protein patterns with statistically significant alignments of multiple sequences , 1999, Bioinform..

[46]  L. Stevens,et al.  The microRNA pathway regulates the temporal pattern of Notch signaling in Drosophila follicle cells , 2011, Development.

[47]  C. Glen,et al.  Foraging modes of Mesozoic birds and non-avian theropods , 2007, Current Biology.

[48]  D. Catalucci,et al.  Jcb: Article , 2022 .

[49]  W. Deng,et al.  Notch signaling and developmental cell-cycle arrest in Drosophila polar follicle cells. , 2009, Molecular biology of the cell.

[50]  C. Cummings,et al.  The daughterless gene functions together with Notch and Delta in the control of ovarian follicle development in Drosophila. , 1994, Development.

[51]  A. Spradling.  Germline cysts: Communes that work , 1993, Cell.

[52]  M. Ashburner,et al.  Sequential gene activation by ecdysone in polytene chromosomes of Drosophila melanogaster. II. The effects of inhibitors of protein synthesis. , 1976, Developmental biology.

[53]  A. Garcı́a-Bellido,et al.  Activation and function of Notch at the dorsal-ventral boundary of the wing imaginal disc. , 1996, Development.

[54]  L. Restifo,et al.  Mutations in a steroid hormone-regulated gene disrupt the metamorphosis of the central nervous system in Drosophila. , 1991, Developmental biology.

[55]  N. Perrimon,et al.  Mechanism of activation of the Drosophila EGF Receptor by the TGFalpha ligand Gurken during oogenesis. , 2002, Development.

[56]  Y. Yoo,et al.  Cooperative and Antagonistic Contributions of Two Heterochromatin Proteins to Transcriptional Regulation of the Drosophila Sex Determination Decision , 2011, PLoS genetics.

[57]  S. Bray,et al.  A model Notch response element detects Suppressor of Hairless–dependent molecular switch , 2001, Current Biology.

[58]  S. Artavanis-Tsakonas,et al.  The involvement of the Notch locus in Drosophila oogenesis. , 1992, Development.

[59]  V. Bedian,et al.  Differential expression of Broad-Complex transcription factors may forecast tissue-specific developmental fates during Drosophila metamorphosis. , 1994, Development.

[60]  Ilan Davis,et al.  The Salvador-Warts-Hippo Pathway Is Required for Epithelial Proliferation and Axis Specification in Drosophila , 2007, Current Biology.