卫星细胞非对称性扩增如何调控颅颌面肌肉再生缺乏深入的研究。申请人在颅颌面肌肉再生的前期研究中发现，卫星细胞可能经Myostatin通路非对称性扩增调控颅颌面肌肉再生。本项目拟首先筛选单肌纤维培养中非对称性扩增的卫星细胞，分析其中Myostatin-ERK通路信号分子的表达情况；通过相关性分析和功能验证，明确Erk1/2和Aurka在卫星细胞非对称性扩增中的作用；通过免疫共沉淀和邻位连接技术，探索Aurka与Myostatin的相互作用关系；进一步通过PABPN1-/-小鼠模型进行功能验证，借助SMASH软件分析颅颌面肌肉再生的表现，阐明Myostatin-ERK-Aurka通路的信号分子在体内表达规律和功能状态。本项目拟通过深入探索卫星细胞经非对称性扩增调控颅颌面肌肉再生的机制，为颅颌面肌肉再生的治疗提供新的思路，为生物治疗在颅颌面肌肉再生的精准应用奠定基础。

Abstract: Congenital deformities in the craniofacial region frequently inflicts loss on muscle tissue,resulting in refractory craniofacial muscle deficiency. Developing biotherapies to expand muscle bulk will hopefully update the treatment protocol.The prerequisite of bringing craniofacial muscle regeneration to clinical use is to understand the underlying mechanism. Satellite cell initiates and controls cranifacial muscle growth and regeneration.Asymetric division plays a critical role in satellite cell-mediated muscle regeneration. But there is a lack of investigation into the mechanism of how satellite cell regulates craniofacial regeneration via asymmetric division. Based on our previous study of the unique property in craniofacial muscle regeneration, we propose that Myostatin could mediate craniofacial regeneration via satellite cell asymmetric division. In this study, we plan to focus on the asymmetric satellite cells in single myofiber culture and analyze the expression level of core components in Myostatin signaling pathway via RNA-seq. Then we will figure out the roles of Myostatin and ERK1/2 in satellite cell asymmetric division by in-vitro and in-vivo functional test. Using co-immunoprecipitation and proximity ligation assay, we can probe into the interaction between ERK1/2 and Aurka, which are supposed to be the downstream effectors of Myostatin sigalling. Furthermore, animal models of mdx and PANBP1 transgenic mice will be applied to functionally test the role of Myostatin-ERK1/2-Aurka in craniofacial muscle regeneration. This program aims to uncover the molecular mechanism of satellite cell asymmetric division in craniofacial muscle regeneration, which will hopefully open new avenues in updating treatment protocols dealing with craniofacial muscle deficiency.