Neural crest and periderm-specific requirements ofIrf6during neural tube and craniofacial development

Abstract

IRF6is a key genetic determinant of syndromic and non-syndromic cleft lip and palate. The ability to interrogate post-embryonic requirements ofIrf6has been hindered, as globalIrf6ablation in the mouse causes neonatal lethality. Prior work analyzingIrf6in mouse models defined its role in the embryonic surface epithelium and periderm where it is required to regulate cell proliferation and differentiation. Several reports have also describedIrf6gene expression in other cell types, such as muscle, and neuroectoderm. However, analysis of a functional role in non-epithelial cell lineages has been incomplete due to the severity and lethality of theIrf6knockout model and the paucity of work with a conditionalIrf6allele. Here we describe the generation and characterization of a newIrf6floxed mouse model and analysis ofIrf6ablation in periderm and neural crest lineages. This work found that loss ofIrf6in periderm recapitulates a mildIrf6null phenotype, suggesting thatIrf6-mediated signaling in periderm plays a crucial role in regulating embryonic development. Further, conditional ablation ofIrf6in neural crest cells resulted in an anterior neural tube defect of variable penetrance. The generation of this conditionalIrf6allele allows for new insights into craniofacial development and new exploration into the post-natal role ofIrf6.