Role of WNT Signaling in Craniofacial Muscle Development

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 DESCRIPTION (provided by applicant): Craniofacial malformations are relatively common human birth defects. The purpose of this study is to understand the cell-fate determination of craniofacial muscle cells during embryogenesis. This work will significantly contribute to the understanding of normal and abnormal human development because mouse muscle development is similar to that of humans. Furthermore, the knowledge we gain from this study will help to prevent and/or alleviate the suffering of those afflicted with craniofacial malformatin. In this application, we will define the molecular and cellular mechanisms of WNT/ß-catenin signaling during craniofacial muscle development. The goal of this project is to illuminate the molecular and cellular mechanisms of WNT/ß-catenin signaling during craniofacial muscle development. The WNT/ß-catenin signaling pathway (Wingless in Drosophila) is an evolutionarily conserved signaling pathway that is important for many developmental and morphogenic processes including cell proliferation, differentiation, and maturation; however, it is not clear how WNT/ß-catenin signaling is involved in regulating craniofacial muscle development. Consistent with essential roles of WNT/ß-catenin signaling in muscle development, mutations in genes involved in WNT/ß-catenin signaling cascades result in muscular disorders. We hypothesize that WNT/ß-catenin signaling determines the fate of muscle cells. Our specific aims are to 1) examine the roles of WNT/ß-catenin signaling in mesoderm- derived muscle cells in regulating craniofacial muscle development by controlling muscle cell proliferation, differentiation, and maturation/maintenance; and, 2) investigate the roles of WNT/ß-catenin signaling in CNC- derived cells in regulating craniofacial muscle development through cell-cell interactions. This study will provide insights into muscular disorders caused by mutations in genes involved in WNT/ß-catenin signaling pathway and help to develop possible strategies for accelerating craniofacial muscle regeneration.