Harnessing population genetics and animal models to uncover the genetics of skin scarring.

Skin wound healing is a complex process that requires the orchestrated response of several different cell types to repair the damaged tissue and restore function. Superficial skin wounds tend to heal within days. However, larger and deeper wounds such as those caused by trauma or surgery generally heal by leaving a scar, which can impact tissue function. Scars can be debilitating, painful, and can significantly impair function. New developments to prevent and treat scarring require a deeper understanding of the cellular and molecular mechanisms associated with wound healing and scarring. Most of our current understanding of the genetics of wound healing comes from studies in animal models. However, population health approaches combined with experimental validation in animal models offer new opportunities to harness natural variability in wound repair outcomes in the population and identify new relevant biology controlling different aspects of repair and scarring in a different way. These approaches have the potential to reveal association between genetic loci and wound phenotypes in humans. Complementary experimental studies in animal models can help to validate these candidate genes and our understanding of the underlying mechanisms. In this non-systematic review, we propose the application of strategies using population health/genetics together with zebrafish models of wounding to specifically study skin scarring. We discuss potential pitfalls and strengths of the combined and complementary use of population health approaches and animal models for the identification and validation of new genes involved in skin repair, and in particular, scarring.