Role of WNT Signaling in Craniofacial Muscle Development

 描述(申请人提供)：颅面畸形是比较常见的人类先天缺陷。本研究的目的是了解胚胎发育过程中颅面肌细胞命运的决定。这项工作将大大有助于理解人类的正常和异常发育，因为老鼠肌肉的发育与人类相似。此外，我们从这项研究中获得的知识将有助于预防和/或减轻头面部畸形患者的痛苦。在这一应用中，我们将确定WNT/？-catenin信号在头面部肌肉发育过程中的分子和细胞机制。本项目的目的是阐明WNT/？连环蛋白信号在头面部肌肉发育过程中的分子和细胞机制。Wnt/？-catenin信号通路(在果蝇中为Wingless)是一种进化上保守的信号通路，对许多发育和形态发生过程包括细胞增殖、分化和成熟都是重要的；然而，它是 尚不清楚WNT/？-catenin信号如何参与调节头面部肌肉的发育。与WNT/？-catenin信号在肌肉发育中的重要作用一致，参与WNT/？-catenin信号级联反应的基因突变会导致肌肉疾病。我们假设Wnt/？-catenin信号决定了肌肉细胞的命运。我们的具体目标是：1)研究中胚层来源的肌肉细胞中的WNT/？-catenin信号通过控制肌肉细胞的增殖、分化和成熟/维持来调节头面部肌肉的发育；2)研究Cnc来源的细胞中的Wnt/？-catenin信号在通过细胞-细胞相互作用调节头面部肌肉发育中的作用。这项研究将为WNT/？-catenin信号通路相关基因突变引起的肌肉疾病提供深入的见解，并有助于开发促进颅面肌再生的可能策略。

 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.