Perfect wound healing in the keratin 8 deficient mouse embryo.
It is generally believed that the strength and structural integrity of both adult and embryonic epithelia comes, at least in part, from their internal cytoskeletal network of keratin filaments and associated cell:cell junctions. Indeed, recent keratin depletion experiments in Xenopus suggest that the capacity of embryonic epithelia to undergo natural morphogenetic movements such as gastrulation, or artificially triggered epithelial movements such as wound closure, are severely compromised in the absence of the predominant embryonic keratin, K8 [Torpey et al., 1992: Nature 357:413-415; Klymkowsky et al., 1992: Proc. Natl. Acad. Sci. USA 89:8736-8740]. These experiments contrast with studies of genetically K8 deficient mouse embryos which undergo gastrulation quite normally and, dependent upon background strain, can survive until beyond birth [Baribault et al., 1993: Genes Dev. 7:1191-1202; Baribault et al., 1994: Genes Dev. 8:2964-2973], but to date no wound healing investigations have been carried out on mK8-mice. In this article, we report our studies of healing in embryonic day 11.5 mouse embryos, wounded by amputation of the hindlimb bud and then cultured in roller bottles. In wild-type embryos, wound closure puts severe strain on the embryonic epidermis since it is under tension and gapes immediately upon wounding; subsequently, epithelial cells tug on one another by means of an actin purse-string in order to close the defect. Even given these extremely challenging conditions, we show here that the mK8- epidermis performs no differently from wild-type epidermis, assembling an actin purse-string in the wound marginal cells and closing the wound with identical timecourse to its wild-type counterpart.
Brock
J
J
Department of Anatomy, University College London, United Kingdom.
McCluskey
J
J
Baribault
H
H
Martin
P
P
D000199:Actins / Q000032:analysis; D000671:Amputation, Surgical; D000818:Animals; D006614:Hindlimb; D007633:Keratins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018878:Limb Buds; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology*
D000199:Actins; D007633:Keratins