title: Ion channels contribute to the regulation of cell sheet forces during Drosophila dorsal closure.
abstract: We demonstrate that ion channels contribute to the regulation of dorsal closure in Drosophila, a model system for cell sheet morphogenesis. We find that Ca(2+) is sufficient to cause cell contraction in dorsal closure tissues, as UV-mediated release of caged Ca(2+) leads to cell contraction. Furthermore, endogenous Ca(2+) fluxes correlate with cell contraction in the amnioserosa during closure, whereas the chelation of Ca(2+) slows closure. Microinjection of high concentrations of the peptide GsMTx4, which is a specific modulator of mechanically gated ion channel function, causes increases in cytoplasmic free Ca(2+) and actomyosin contractility and, in the long term, blocks closure in a dose-dependent manner. We identify two channel subunits, ripped pocket and dtrpA1 (TrpA1), that play a role in closure and other morphogenetic events. Blocking channels leads to defects in force generation via failure of actomyosin structures, and impairs the ability of tissues to regulate forces in response to laser microsurgery. Our results point to a key role for ion channels in closure, and suggest a mechanism for the coordination of force-producing cell behaviors across the embryo.
authors.affiliation: Department of Biology, Duke University, Durham, NC 27708, USA.
authors.forename: Ginger L
authors.initials: GL
authors.lastname: Hunter
authors.forename: Janice M
authors.initials: JM
authors.lastname: Crawford
authors.forename: Julian Z
authors.initials: JZ
authors.lastname: Genkins
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Kiehart
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis; D009154:Mutation; D010455:Peptides / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism; D013111:Spider Venoms / Q000494:pharmacology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; C411249:MTx4 protein, Grammostola spatulata; D010455:Peptides; D015222:Sodium Channels; D013111:Spider Venoms; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C475684:TrpA1 protein, Drosophila; C111894:rpk protein, Drosophila; D000205:Actomyosin; D002118:Calcium
keywords: Dorsal closure; Ion channels; Morphogenesis