Interferon Regulatory Factor 6, a novel transcriptional regulator of embryonic development and wound healing

Abstract

Cleft lip and palate (CLP) constitutes the second most common congenital birth defects in the US. This complex trait results from a disruption of the highly coordinated growth, migration and fusion of facial prominences during early embryological development. Evidence from genetic studies, animal models, and expression data suggest a variety of candidate genes for CLP. Amongst them, Interferon Regulatory Factor 6 (IRF6) is unique because DNA variation in this gene both causes and contributes significant risk for orofacial clefts. IRF6. Loss of function of IRF6 in human causes two orofacial syndromes, Van der Woude (VWS) and Popliteal Pterygium. In the mouse, deletion of Irf6 leads to craniofacial anomalies, as well as limb and cutaneous defects. These data support a role for Irf6 in embryonic development. Recent clinical chart review of patients with orofacial clefts indicated that patients with VWS were more likely to develop wound complications after corrective cleft surgery compared to patients with an isolated cleft, suggesting that IRF6 plays an additional role in wound healing. We took advantage of the murine model to culture keratinocytes from wildtype and Irf6‐deficient animals. Our in vitro data indicate a delay in scratch closure in the absence of Irf6. Potential molecular mechanisms beyond this observation will be presented, along with novel in vivo wound healing models.DE16215 and AR055313