Recapitulation of morphogenetic cell shape changes enables wound re-epithelialisation

Abstract

Wound repair is a fundamental, conserved mechanism for maintaining tissue homeostasis and shares many parallels with embryonic morphogenesis. Small wounds in simple epithelia rapidly assemble a contractile actomyosin cable at their leading edge, as well as dynamic filopodia that finally knit the wound edges together. Most studies of wound re-epithelialisation have focused on the actin machineries that assemble in the leading edge of front row cells and that resemble the contractile mechanisms that drive morphogenetic episodes, including Drosophila dorsal closure, but, clearly, multiple cell rows back must also contribute for efficient repair of the wound. Here, we examine the role of cells back from the wound edge and show that they also stretch towards the wound and cells anterior-posterior to the wound edge rearrange their junctions with neighbours to drive cell intercalation events. This process in anterior-posterior cells is active and dependent on pulses of actomyosin that lead to ratcheted shrinkage of junctions; the actomyosin pulses are targeted to breaks in the cell polarity protein Par3 at cell vertices. Inhibiting actomyosin dynamics back from the leading edge prevents junction shrinkage and inhibits the wound edge from advancing. These events recapitulate cell rearrangements that occur during germband extension, in which intercalation events drive the elongation of tissues.

Re-epithelialization of cutaneous wounds in adult zebrafish uses a combination of mechanisms at play during wound closure in embryonic and adult mammals

“…However, the latter seems to have a rather weak and, possibly, indirect impact on wound closure, promoting radial cell intercalations, which could be compromised when cells were elongated in random directions. Interestingly, similar cell elongations have been reported for superficial skin cells during wound closure in mouse, zebrafish and Drosophila embryos (Gault et al, 2014;Martin and Parkhurst, 2004;McCluskey and Martin, 1995;Razzell et al, 2014) and mutant analyses have unravelled an essential role of the PCP pathway for embryonic wound closure in mouse (Caddy et al, 2011). Together, our data indicate that wound re-epithelialization of adult zebrafish uses a combination of mechanisms employed during embryonic and adult wound closure in mammals.…”

Periderm prevents pathological epithelial adhesions during embryogenesis

“…Notably, all 3 mutant strains fail to develop normal periderm, with multiple membrane protrusions forming on the apical surface of the exposed basal cells. These observations are reminiscent of the morphological events observed during dorsal closure in Drosophila embryos and in wound closure (33,34). Together, these findings indicate that the presence of periderm prevents exposed, adhesion-competent, basal cells from actively contacting one another: in essence, periderm acts as a protective "Teflon" coat.…”

Endocytosis-dependent coordination of multiple actin regulators is required for wound healing

“…For instance, it has recently been demonstrated that wound closure in Drosophila embryos involves cell rearrangements behind the wound edge, which are similar to those that occur during germband extension (Levayer et al, 2011;Razzell et al, 2014). Because germband extension cell rearrangements require the endocytosis-dependent remodeling of AJs, it is likely that those occurring during wound healing also do.…”