title: The Drosophila shark tyrosine kinase is required for embryonic dorsal closure.
abstract: Dorsal closure (DC) in the Drosophila embryo requires the coordinated interaction of two different functional domains of the epidermal cell layer-the leading edge (LE) and the lateral epidermis. In response to activation of a conserved c-Jun amino-terminal kinase (JNK) signaling module, the dorsal-most layer of cells, which constitute the LE of the stretching epithelial sheet, secrete Dpp, a member of the TGFbeta superfamily. Dpp and other LE cell-derived signaling molecules stimulate the bilateral dorsal elongation of cells of the dorsolateral epidermis over the underlaying amnioserosa and the eventual fusion of their LEs along the dorsal midline. We have found that flies bearing a Shark tyrosine kinase gene mutation, shark(1), exhibit a DC-defective phenotype. Dpp fails to be expressed in shark(1) mutant LE cells. Consistent with these observations, epidermal-specific reconstitution of shark function or overexpression of an activated form of c-Jun in the shark(1) mutant background, rescues the DC defect. Thus, Shark regulates the JNK signaling pathway leading to Dpp expression in LE cells. Furthermore, constitutive activation of the Dpp pathway throughout the epidermis fails to rescue the shark(1) DC defect, suggesting that Shark may function in additional pathways in the LE and/or lateral epithelium.
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, The Bronx, New York 10461, USA.
authors.forename: R
authors.initials: R
authors.lastname: Fernandez
authors.forename: F
authors.initials: F
authors.lastname: Takahashi
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: R
authors.initials: R
authors.lastname: Steward
authors.forename: D
authors.initials: D
authors.lastname: Stein
authors.forename: E R
authors.initials: ER
authors.lastname: Stanley
mesh_terms: D000818:Animals; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000502:physiology; D004817:Epidermis / Q000196:embryology; D005020:Ethyl Methanesulfonate; D005260:Female; D019476:Insect Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology*; D016296:Mutagenesis; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D014960:X Chromosome
chemical_list: D029721:Drosophila Proteins; D019476:Insect Proteins; C064196:dpp protein, Drosophila; D005020:Ethyl Methanesulfonate; C092552:Shark protein, Drosophila; D011505:Protein-Tyrosine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases