Molecular Control of the Migratory Phase During Cutaneous Wound Healing

Superficial cutaneous injuries occur on a huge scale across the globe; while most will resolve without intervention or any lasting damage, many will experience complications that arise through delayed healing or as a consequence of the skins protective barrier being breached. The migration of cutaneous cells across a wound site is a crucial factor in establishing permanent restoration of the skins integrity. This study provides insight into molecular events that facilitate the migratory ability of cutaneous cells during this phase of the healing process. Through subcellular analysis, molecular manipulation and various imaging techniques of in vivo and in vitro wound models, this project has discovered that the autophagy pathway is activated in response to injury and also that the resultant autophagosomes form in a polarised manner towards the trailing end of migrating keratinocytes. Results indicate that initiation of autophagy is responsive to Wnt5a signals secreted by several cell types within the wound site and these signals must pass through Frizzled 3 receptors and Rho-associated protein kinase to activate nucleation of phagophore membranes. This study also develops and tests the use of novel wound healing platforms in the form of ex vivo murine models and 3-dimensional full-thickness human skin equivalents to help assess the role of autophagy specifically in the context of wound healin