Drosophila embryos close epithelial wounds using a combination of cellular protrusions and an actomyosin purse string

Abstract

SummaryThe repair of injured tissue must occur rapidly to prevent microbial invasion and maintain tissue integrity. Epithelial tissues in particular, which serve as a barrier against the external environment, must repair efficiently in order to restore their primary function. Here we analyze the effect of different parameters on the epithelial wound repair process in the late stage Drosophila embryo using in vivo wound assays, expression of cytoskeleton and membrane markers, and mutant analysis. We define four distinct phases in the repair process, expansion, coalescence, contraction and closure, and describe the molecular dynamics of each phase. Specifically, we find that myosin, E-cadherin, Echinoid, the plasma membrane, microtubules and the Cdc42 small GTPase respond dynamically during wound repair. We demonstrate that perturbations of each of these components result in specific impairments to the wound healing process. Our results show that embryonic epithelial wound repair is mediated by two simultaneously acting mechanisms: crawling driven by cellular protrusions and actomyosin ring contraction along the leading edge of the wound.

Automated multidimensional image analysis reveals a role for Abl in embryonic wound repair

“…β-catenin was rapidly depleted from the wound margin and accumulated at tricellular vertices between wounded and adjacent cells. This distribution is similar to that of other junctional proteins, such as E-cadherin (Brock et al, 1996;Abreu-Blanco, 2012) and α-catenin (Wood et al, 2002). The depletion of β-catenin from the wound margin might facilitate disassembly of the junctions between wounded and adjacent cells.…”

“…In wound closure, the junctional molecules E-cadherin and α-catenin are depleted from the wound perimeter and accumulate at tricellular vertices between wounded and adjacent cells (Abreu-Blanco et al, 2012;Brock et al, 1996;Wood et al, 2002). We used MEDUSA to determine whether β-catenin was also redistributed during wound closure.…”

“…This actomyosin cable contracts, serving as a 'purse string' that contributes to wound closure (Fernandez-Gonzalez and Zallen, 2013). The junctional molecules E-cadherin and α-catenin are depleted from the interfaces between wounded and adjacent cells, and accumulate at tricellular vertices at the wound margin (Abreu-Blanco et al, 2012;Brock et al, 1996;Wood et al, 2002). The redistribution of junctional proteins during wound repair is thought to provide discrete anchor points for the assembly of a contractile purse string around the wound.…”

“…Drosophila has emerged as a model to investigate embryonic wound repair (Abreu-Blanco et al, 2012FernandezGonzalez and Zallen, 2013;Kiehart et al, 2000;Pickering et al, 2013;Wood et al, 2002). The genetic tractability of Drosophila allows the use of genetic screening to identify novel molecules implicated in embryonic wound healing (Campos et al, 2010;Juarez et al, 2011).…”

Tension regulates myosin dynamics during Drosophila embryonic wound repair

“…During embryonic wound repair, actin and myosin are polarized in the cells adjacent to the wound, accumulating at the interface with the wounded cells and forming a supracellular cable around the wound (Martin and Lewis, 1992;Brock et al, 1996;Kiehart et al, 2000;Davidson et al, 2002;Kofron et al, 2002;Wood et al, 2002;Clark et al, 2009). The actomyosin cable contracts (Fernandez-Gonzalez and Zallen, 2013), serving as a purse string that coordinates the migratory behaviours of the cells adjacent to the wound (Brock et al, 1996;Wood et al, 2002;Abreu-Blanco et al, 2012). Embryonic wound closure can last minutes or hours, with total myosin levels at the purse string remaining relatively constant (Fernandez-Gonzalez and Zallen, 2013).…”