Embryonic wound healing by apical contraction and ingression in Xenopus laevis

Abstract

We have characterized excisional wounds in the animal cap of early embryos of the frog Xenopus laevis and found that these wounds close accompanied by three distinct processes: (1) the assembly of an actin purse-string in the epithelial cells at the wound margin, (2) contraction and ingression of exposed deep cells, and (3) protrusive activity of epithelial cells at the margin. Microsurgical manipulation allowing fine control over the area and depth of the wound combined with videomicroscopy and confocal analysis enabled us to describe the kinematics and challenge the mechanics of the closing wound. Full closure typically occurs only when the deep, mesenchymal cell-layer of the ectoderm is left intact; in contrast, when deep cells are removed along with the superficial, epithelial cell-layer of the ectoderm, wounds do not close. Actin localizes to the superficial epithelial cell-layer at the wound margin immediately after wounding and forms a contiguous "purse-string" in those cells within 15 min. However, manipulation and closure kinematics of shaped wounds and microsurgical cuts made through the purse-string rule out a major force-generating role for the purse-string. Further analysis of the cell behaviors within the wound show that deep, mesenchymal cells contract their apical surfaces and ingress from the exposed surface. High resolution time-lapse sequences of cells at the leading edge of the wound show that these cells undergo protrusive activity only during the final phases of wound closure as the ectoderm reseals. We propose that assembly of the actin purse-string works to organize and maintain the epithelial sheet at the wound margin, that contraction and ingression of deep cells pulls the wound margins together, and that protrusive activity of epithelial cells at the wound margin reseals the ectoderm and re-establishes tissue integrity during wound healing in the Xenopus embryonic ectoderm.

Transcriptional regulation of Profilin during wound closure in Drosophila larvae

“…Second they do not appear to be locally contractile given that the cells behind prominent concentrations do not obviously taper toward the wound. This is similar to what has been observed in the embryonic Xenopus epithelium where actin cables form but differently shaped wounds do not round up as would be expected from cable contraction (Davidson et al, 2002). Thus it would appear that in larvae the actin concentrated at the wound edge primarily facilitates process extension into the wound gap.…”

Lysophosphatidic acid signaling controls cortical actin assembly and cytoarchitecture in Xenopus embryos

“…Brock et al first described the formation of an actinomyosin purse-string that is assembled rapidly to provide the driving force to close embryonic wounds (Brock et al, 1996). However, previous work in Xenopus embryos suggests that in superficial wounds, where the deep layer of cells is not breached, the purse-string does not provide the driving force for wound closure (Davidson et al, 2002). Instead, contraction and ingression of the deep cells may pull the wound closed.…”

Apical constriction: themes and variations on a cellular mechanism driving morphogenesis

“…Apical constriction of individual cells can contribute to cell ingression from epithelial tissues, sometimes as a step in an epithelialmesenchymal transition (EMT) (Anstrom, 1992;Nance and Priess, 2002;Harrell and Goldstein, 2011;Williams et al, 2012). Apical constriction is also associated with the extrusion of apoptotic or delaminating cells (Toyama et al, 2008;Slattum et al, 2009;Marinari et al, 2012) and wound contraction and healing (Davidson et al, 2002;Antunes et al, 2013). Thus, apical constriction remodels epithelia in a variety of ways to achieve proper tissue shape and structure.…”