Wound healing and inflammation: embryos reveal the way to perfect repair.
Tissue repair in embryos is rapid, efficient and perfect and does not leave a scar, an ability that is lost as development proceeds. Whereas adult wound keratinocytes crawl forwards over the exposed substratum to close the gap, a wound in the embryonic epidermis is closed by contraction of a rapidly assembled actin purse string. Blocking assembly of this cable in chick and mouse embryos, by drugs or by inactivation of the small GTPase Rho, severely hinders the re-epithelialization process. Live studies of epithelial repair in GFP-actin-expressing Drosophila embryos reveal actin-rich filopodia associated with the cable, and although these protrusions from leading edge cells appear to play little role in epithelial migration, they are essential for final zippering of the wound edges together-inactivation of Cdc42 prevents their assembly and blocks the final adhesion step. This wound re-epithelialization machinery appears to recapitulate that used during naturally occurring morphogenetic episodes as typified by Drosophila dorsal closure. One key difference between embryonic and adult repair, which may explain why one heals perfectly and the other scars, is the presence of an inflammatory response at sites of adult repair where there is none in the embryo. Our studies of repair in the PU. 1 null mouse, which is genetically incapable of raising an inflammatory response, show that inflammation may indeed be partly responsible for scarring, and our genetic studies of inflammation in zebrafish (Danio rerio) larvae suggest routes to identifying gene targets for therapeutically modulating the recruitment of inflammatory cells and thus improving adult healing.
Department of Anatomny and Developmental Biology, University College London, Gower Street, London WCIE 6BT, UK.
Michael J
MJ
Redd
Lisa
L
Cooper
Will
W
Wood
Brian
B
Stramer
Paul
P
Martin
D000199:Actins / Q000502:physiology*; D000818:Animals; D002642:Chick Embryo; D004330:Drosophila; D004625:Embryo, Nonmammalian / Q000502:physiology; D004848:Epithelium / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis; D014945:Wound Healing / Q000502:physiology*; D015027:Zebrafish
D000199:Actins