Wound healing recapitulates morphogenesis in Drosophila embryos.
The capacity to repair a wound is a fundamental survival mechanism that is activated at any site of damage throughout embryonic and adult life. To study the cell biology and genetics of this process, we have developed a wounding model in Drosophila melanogaster embryos that allows live imaging of rearrangements and changes in cell shape, and of the cytoskeletal machinery that draws closed an in vivo wound. Using embryos expressing green fluorescent protein (GFP) fusion proteins, we show that two cytoskeletal-dependent elements -- an actin cable and dynamic filopodial/lamellipodial protrusions -- are expressed by epithelial cells at the wound edge and are pivotal for repair. Modulating the activities of the small GTPases Rho and Cdc42 demonstrates that these actin-dependent elements have differing cellular functions, but that either alone can drive wound closure. The actin cable operates as a 'purse-string' to draw the hole closed, whereas filopodia are essential for the final 'knitting' together of epithelial cells at the end of repair. Our data suggest a more complex model for epithelial repair than previously envisaged and highlight remarkable similarities with the well-characterized morphogenetic movement of dorsal closure in Drosophila.
Wood
William
W
Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
Jacinto
Antonio
A
Grose
Richard
R
Woolner
Sarah
S
Gale
Jonathan
J
Wilson
Clive
C
Martin
Paul
P
D000199:Actins / Q000737:chemistry; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004847:Epithelial Cells / Q000378:metabolism; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D009024:Morphogenesis; D009154:Mutation; D011554:Pseudopodia / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014945:Wound Healing; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000199:Actins; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins