title: Multiple signaling pathways and a selector protein sequentially regulate Drosophila wing development.
abstract: Drosophila wing development is a useful model to study organogenesis, which requires the input of selector genes that specify the identity of various morphogenetic fields (Weatherbee, S. D. and Carroll, S. B. (1999) Cell 97, 283-286) and cell signaling molecules. In order to understand how the integration of multiple signaling pathways and selector proteins can be achieved during wing development, we studied the regulatory network that controls the expression of Serrate (Ser), a ligand for the Notch (N) signaling pathway, which is essential for the development of the Drosophila wing, as well as vertebrate limbs. Here, we show that a 794 bp cis-regulatory element located in the 3' region of the Ser gene can recapitulate the dynamic patterns of endogenous Ser expression during wing development. Using this enhancer element, we demonstrate that Apterous (Ap, a selector protein), and the Notch and Wingless (Wg) signaling pathways, can sequentially control wing development through direct regulation of Ser expression in early, mid and late third instar stages, respectively. In addition, we show that later Ser expression in the presumptive vein cells is controlled by the Egfr pathway. Thus, a cis-regulatory element is sequentially regulated by multiple signaling pathways and a selector protein during Drosophila wing development. Such a mechanism is possibly conserved in the appendage outgrowth of other arthropods and vertebrates.
authors.affiliation: Department of Biology, University of Rochester, Rochester, NY 14627, USA.
authors.forename: Shian-Jang
authors.initials: SJ
authors.lastname: Yan
authors.forename: Yi
authors.initials: Y
authors.lastname: Gu
authors.forename: Willis X
authors.initials: WX
authors.lastname: Li
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fleming
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D005246:Feedback; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D060850:LIM-Homeodomain Proteins; D007814:Larva / Q000254:growth & development; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014921:Wings, Animal / Q000254:growth & development; D051155:Wnt1 Protein
chemical_list: D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D060850:LIM-Homeodomain Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D011518:Proto-Oncogene Proteins; D051880:Receptors, Notch; C000606278:Ser protein, Drosophila; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C074459:ap protein, Drosophila; C074622:wg protein, Drosophila; D004247:DNA