Role of WNT Signaling in Craniofacial Muscle Development

 描述（由申请人提供）：颅面畸形是相对常见的人类出生缺陷。本研究旨在了解颅面肌细胞在胚胎发生过程中的细胞命运决定。这项工作将大大有助于了解正常和异常的人类发育，因为小鼠肌肉发育与人类相似。此外，我们从这项研究中获得的知识将有助于预防和/或减轻颅面畸形患者的痛苦。在本申请中，我们将定义颅面肌发育过程中WNT/β-连环蛋白信号传导的分子和细胞机制。本项目的目标是阐明颅面肌发育过程中WNT/β-catenin信号传导的分子和细胞机制。WNT/β-连环蛋白信号通路（果蝇中的无翅）是进化上保守的信号通路，其对于许多发育和形态发生过程（包括细胞增殖、分化和成熟）是重要的;然而， 目前尚不清楚WNT/β-catenin信号是如何参与调节颅面肌发育的。与WNT/β-连环蛋白信号传导在肌肉发育中的基本作用一致，参与WNT/β-连环蛋白信号传导级联的基因突变导致肌肉疾病。我们推测WNT/β-catenin信号决定了肌肉细胞的命运。我们的具体目标是1）检查中胚层来源的肌细胞中的WNT/β-连环蛋白信号传导在通过控制肌细胞增殖、分化和成熟/维持来调节颅面肌发育中的作用;以及2）研究CNC来源的细胞中的WNT/β-连环蛋白信号传导在通过细胞-细胞相互作用来调节颅面肌发育中的作用。这项研究将为WNT/β-catenin信号通路相关基因突变引起的肌肉疾病提供见解，并有助于开发加速颅面肌肉再生的可能策略。

 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.