Whole-Genome Analysis of Dorsal-Ventral Patterning in the Drosophila Embryo

The maternal Dorsal regulatory gradient initiates the differentiation of several tissues in the early Drosophila embryo. Whole-genome microarray assays identified as many as 40 new Dorsal target genes, which encode a broad spectrum of cell signaling proteins and transcription factors. Evidence is presented that a tissue-specific form of the NF-Y transcription complex is essential for the activation of gene expression in the mesoderm. Tissue-specific enhancers were identified for new Dorsal target genes, and bioinformatics methods identified conserved cis-regulatory elements for coordinately regulated genes that respond to similar thresholds of the Dorsal gradient. The new Dorsal target genes and enhancers represent one of the most extensive gene networks known for any developmental process.

[1]  D Kosman,et al.  The dorsal morphogen gradient regulates the mesoderm determinant twist in early Drosophila embryos. , 1991, Genes & development.

[2]  M. Levine,et al.  The dorsal morphogen is a sequence-specific DNA-binding protein that interacts with a long-range repression element in drosophila , 1991, Cell.

[3]  B. Mccarthy,et al.  Regulation of Drosophila alpha- and beta-tubulin genes during development. , 1984, Developmental biology.

[4]  K. Anderson,et al.  Dominant and recessive mutations define functional domains of Toll, a transmembrane protein required for dorsal-ventral polarity in the Drosophila embryo. , 1991, Genes & development.

[5]  D. Tautz,et al.  A non-radioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals translational control of the segmentation gene hunchback , 1989, Chromosoma.

[6]  D Kosman,et al.  Establishment of the mesoderm-neuroectoderm boundary in the Drosophila embryo. , 1991, Science.

[7]  Peter W. Markstein,et al.  Genome-wide analysis of clustered Dorsal binding sites identifies putative target genes in the Drosophila embryo , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[8]  E. Hafen,et al.  An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control , 2001, Current Biology.

[9]  S. Higashijima,et al.  Two FGF-receptor homologues of Drosophila: one is expressed in mesodermal primordium in early embryos. , 1993, Development.

[10]  R. Steward.  Dorsal, an embryonic polarity gene in Drosophila, is homologous to the vertebrate proto-oncogene, c-rel. , 1987, Science.

[11]  K. Anderson,et al.  A conserved signaling pathway: the Drosophila toll-dorsal pathway. , 1996, Annual review of cell and developmental biology.

[12]  Michael Levine,et al.  Dorsal gradient networks in the Drosophila embryo. , 2002, Developmental biology.

[13]  J. Emery,et al.  Dorsal-ventral patterning of the Drosophila embryo depends on a putative negative growth factor encoded by the short gastrulation gene. , 1994, Genes & development.

[14]  G. Martin,et al.  Making a vertebrate limb: new players enter from the wings. , 2001, BioEssays : news and reviews in molecular, cellular and developmental biology.

[15]  J. D. Huang,et al.  The establishment and interpretation of transcription factor gradients in the Drosophila embryo. , 1995, Biochimica et biophysica acta.

[16]  C. Doe,et al.  Dorsoventral patterning in the Drosophila central nervous system: the vnd homeobox gene specifies ventral column identity. , 1998, Genes & development.

[17]  Michael Levine,et al.  Linear signaling in the Toll-Dorsal pathway of Drosophila: activated Pelle kinase specifies all threshold outputs of gene expression while the bHLH protein Twist specifies a subset. , 2002, Development.

[18]  M Hoch,et al.  cis‐acting control elements for Krüppel expression in the Drosophila embryo. , 1990, The EMBO journal.

[19]  Ting-Yi Lin,et al.  Developmental regulation of transcription by a tissue-specific TAF homolog. , 2001, Genes & development.

[20]  Gerald M. Rubin,et al.  The embryonic expression patterns of zfh-1 and zfh-2, two Drosophila genes encoding novel zinc-finger homeodomain proteins , 1991, Mechanisms of Development.

[21]  L H Frank,et al.  A group of genes required for maintenance of the amnioserosa tissue in Drosophila. , 1996, Development.

[22]  Y. Jan,et al.  A new homeobox-containing gene, msh-2, is transiently expressed early during mesoderm formation of Drosophila. , 1990, Development.

[23]  Frédéric Crémazy,et al.  Sox Neuro, a new Drosophila Sox gene expressed in the developing central nervous system , 2000, Mechanisms of Development.

[24]  M. Strigini,et al.  Formation of morphogen gradients in the Drosophila wing. , 1999, Seminars in cell & developmental biology.

[25]  M. Levine,et al.  Regulation of a dpp target gene in the Drosophila embryo. , 1997, Development.

[26]  M. Levine,et al.  Spatial regulation of zerknüllt: a dorsal-ventral patterning gene in Drosophila. , 1989, Genes & development.

[27]  M. Levine,et al.  Threshold responses to the dorsal regulatory gradient and the subdivision of primary tissue territories in the Drosophila embryo. , 1996, Current opinion in genetics & development.

[28]  M. Levine,et al.  dorsal-twist interactions establish snail expression in the presumptive mesoderm of the Drosophila embryo. , 1992, Genes & development.

[29]  M. W. Young,et al.  kuzbanian-mediated cleavage of Drosophila Notch. , 2002, Genes & development.

[30]  T. Jessell.  Neuronal specification in the spinal cord: inductive signals and transcriptional codes , 2000, Nature Reviews Genetics.

[31]  E. Wieschaus,et al.  Hyperactivation of the folded gastrulation pathway induces specific cell shape changes. , 1998, Development.

[32]  M. Taylor,et al.  Drosophila MEF2 is regulated by twist and is expressed in both the primordia and differentiated cells of the embryonic somatic, visceral and heart musculature , 1995, Mechanisms of Development.

[33]  S. Pfaff,et al.  CHAPTER 268 – Signaling Pathways that Regulate Neuronal Specification in the Spinal Cord , 2003 .

[34]  J. D. Engel,et al.  A GATA family transcription factor is expressed along the embryonic dorsoventral axis in Drosophila melanogaster. , 1993, Development.

[35]  M. Leptin,et al.  Identification of novel genes in Drosophila reveals the complex regulation of early gene activity in the mesoderm. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[36]  S. Roth.  Axis Determination: Proteolytic generation of a morphogen , 1994, Current Biology.

[37]  M. Karin,et al.  Signal transduction by tumor necrosis factor and its relatives. , 2001, Trends in cell biology.

[38]  E. Hafen,et al.  Common and distinct roles of DFos and DJun during Drosophila development. , 1997, Science.

[39]  J. Gurdon,et al.  Morphogen gradient interpretation , 2001, Nature.

[40]  S. Roth,et al.  Autonomy and non-autonomy in Drosophila mesoderm determination and morphogenesis. , 1994, Development.

[41]  K. White,et al.  Patterns of Gene Expression During Drosophila Mesoderm Development , 2001, Science.

[42]  R. Baum.  The Molecular Biology: Researchers probe structure and genetics of HTV in effort to understand virus, how it causes AIDS, and weaknesses that might lead to therapies , 1987 .

[43]  M. Levine,et al.  An anteroposterior Dorsal gradient in the Drosophila embryo. , 1997, Genes & development.

[44]  Eric Wieschaus,et al.  A putative cell signal encoded by the folded gastrulation gene coordinates cell shape changes during Drosophila gastrulation , 1994, Cell.

[45]  Robert Tjian,et al.  Requirement of Tissue-Selective TBP-Associated Factor TAFII105 in Ovarian Development , 2001, Science.

[46]  D. Morisato.  Spätzle regulates the shape of the Dorsal gradient in the Drosophila embryo. , 2001, Development.

[47]  L. Stevens,et al.  Spatially Restricted Expression of pipe in the Drosophila Egg Chamber Defines Embryonic Dorsal–Ventral Polarity , 1998, Cell.

[48]  C. Nüsslein-Volhard,et al.  The origin of pattern and polarity in the Drosophila embryo , 1992, Cell.

[49]  S. Crews,et al.  Specification of the Drosophila CNS midline cell lineage: direct control of single-minded transcription by dorsal/ventral patterning genes. , 1998, Gene expression.

[50]  R. Mantovani,et al.  The molecular biology of the CCAAT-binding factor NF-Y. , 1999, Gene.

[51]  N. Perrimon,et al.  DRhoGEF2 encodes a member of the Dbl family of oncogenes and controls cell shape changes during gastrulation in Drosophila. , 1998, Genes & development.

[52]  P. Ingham,et al.  Hedgehog signaling in animal development: paradigms and principles. , 2001, Genes & development.

[53]  D. Wassarman,et al.  Genes Encoding Drosophila melanogaster RNA Polymerase II General Transcription Factors , 2000, The Journal of cell biology.

[54]  C Q Doe,et al.  Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity. , 1998, Genes & development.

[55]  J. Dahlberg,et al.  Molecular biology. , 1977, Science.

[56]  G M Rubin,et al.  Isolation and expression of scabrous, a gene regulating neurogenesis in Drosophila. , 1990, Genes & development.

[57]  C. Rushlow,et al.  The Drosophila dorsal morphogen represses the tolloid gene by interacting with a silencer element , 1994, Molecular and cellular biology.

[58]  J. Natzle.  Regulation of Drosophila ?- and ?-tubulin genes during development*1 , 1984 .

[59]  M. Nirenberg,et al.  Regulatory DNA required for vnd/NK-2 homeobox gene expression pattern in neuroblasts , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[60]  M. Levine,et al.  Race: a drosophila homologue of the angiotensin converting enzyme , 1995, Mechanisms of Development.

[61]  T. Schüpbach,et al.  Versatility in signalling: multiple responses to EGF receptor activation during Drosophila oogenesis. , 1999, Trends in cell biology.

[62]  M. Levine,et al.  The dorsal gradient morphogen regulates stripes of rhomboid expression in the presumptive neuroectoderm of the Drosophila embryo. , 1992, Genes & development.

[63]  M. Levine,et al.  Regulation of even‐skipped stripe 2 in the Drosophila embryo. , 1992, The EMBO journal.

[64]  P. Rakic,et al.  Processing of the notch ligand delta by the metalloprotease Kuzbanian. , 1999, Science.

[65]  M. Levine,et al.  Multiple modes of dorsal‐bHLH transcriptional synergy in the Drosophila embryo. , 1995, The EMBO journal.

[66]  S. Roth,et al.  The role of brinker in mediating the graded response to Dpp in early Drosophila embryos. , 1999, Development.

[67]  E. L. Ferguson,et al.  Morphogen gradients: new insights from DPP. , 1999, Trends in genetics : TIG.

[68]  G. Rubin,et al.  Genetic transformation of Drosophila with transposable element vectors. , 1982, Science.

[69]  W. Gelbart,et al.  Decapentaplegic transcripts are localized along the dorsal‐ventral axis of the Drosophila embryo. , 1987, The EMBO journal.

[70]  D Kosman,et al.  Concentration-dependent patterning by an ectopic expression domain of the Drosophila gap gene knirps. , 1997, Development.

[71]  E. Macagno,et al.  Expression of achaete and scute genes in Drosophila imaginal discs and their function in sensory organ development. , 1989, Genes & development.

[72]  T. Aigaki,et al.  Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway , 2002, The EMBO journal.