title: The small GTPase Rac plays multiple roles in epithelial sheet fusion--dynamic studies of Drosophila dorsal closure.
abstract: The coordinated migration and fusion of epithelial sheets is a crucial morphogenetic tool used on numerous occasions during the normal development of an embryo and re-activated as part of the wound healing response. Drosophila dorsal closure, whereby a hole in the embryonic epithelium is zipped closed late in embryogenesis, serves as an excellent, genetically tractable model for epithelial migration. Using live confocal imaging, we have dissected multiple roles for the small GTPase Rac in this process. We show that constitutive activation of Rac1 leads to excessive assembly of lamellipodia and precocious halting of epithelial sweeping, possibly through premature activation of contact-inhibition machinery. Conversely, blocking Rac activity, either by loss-of-function mutations or expression of dominant negative Rac1, disables the assembly of both actin cable and protrusions by epithelial cells. Movies of mutant embryos show that continued contraction of the amnioserosa is sufficient to draw the epithelial edges towards one another, allowing the zipper machinery to bypass non-functioning regions of leading edge. In addition to illustrating the key role of Rac in organization of leading edge actin, loss-of-function mutants also provide substantive proof that Rac acts upstream in the Jun N-terminal kinase (JNK) cascade to direct epithelial cell shape changes during dorsal closure.
authors.affiliation: Department of Anatomy, University College London, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Woolner
authors.forename: Antonio
authors.initials: A
authors.lastname: Jacinto
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
mesh_terms: D000818:Animals; D048430:Cell Shape / Q000502:physiology; D004330:Drosophila / Q000196:embryology*; D004625:Embryo, Nonmammalian / Q000196:embryology; D004789:Enzyme Activation / Q000502:physiology; D004848:Epithelium / Q000502:physiology*; D049452:Green Fluorescent Proteins; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014741:Video Recording; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein
chemical_list: D009479:Neuropeptides; C484602:Rac1 protein, mouse; D049452:Green Fluorescent Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein