Investigating the Role of the Planar Cell Polarity Pathway in Vertebrate Epidermal Wound Closure

Abstract

Effective and efficient repair of damage incurred by the body is a fundamental capability of living organisms. In the skin, wound closure is achieved by keratinocyte migration, a highly orchestrated process that is not fully understood. Recently, a potential link was identified between the Planar Cell Polarity (PCP) pathway and known signalling cascades essential for wound repair. PCP regulates collective cell movements in a broad range of embryonic morphogenetic processes, including vertebrate convergent extension, that are recapitulated in wound healing. Disruptions to PCP chiefly result in severe birth defects involving incomplete closure of the neural tube, but in some cases PCP mutants also exhibit delayed wound healing. Clear evidence exists for PCP regulation of wound repair, yet its influence has not been well studied in this context. We have optimized two valuable tools, an in vitro and in vivo wound assay, for evaluating PCP in action during healing. Using those wound assays, we present data in support of an instructive role for PCP in mammalian epidermal wound closure. In addition, we offer evidence that the localization of PCP components changes in the wounded state. We propose that this reorientation of cell polarity acts to organize cells at the wound border, thereby coordinating collective cell migration. Future investigations are suggested for describing consistent patterns of PCP reorientation during wounding and determining the specific effect of PCP disruption on cell behavior. Further characterization of PCP as an upstream guide for healing will shed light on the complex ways a group of moving cells communicates in order to make vast changes to the tissue architecture.