FoxG1和Notch信号协同调控内耳干细胞再生耳蜗毛细胞的研究

感音神经性耳聋是耳蜗毛细胞的不可逆损伤造成的。耳蜗Lgr5阳性细胞是内耳干细胞，抑制Notch信号通路可以一定程度上促进毛细胞再生，但效果并不显著。重要转录因子FoxG1调控神经干细胞的增殖与分化，并能与Notch信号通路的关键因子相互作用调控其下游基因。目前FoxG1在调控内耳干细胞方面的作用尚不清楚。本项目将研究FoxG1在内耳干细胞再生毛细胞方面的作用及机制，并通过FoxG1与Notch信号通路协同调控进一步促进内耳干细胞再生毛细胞。拟实现目标：一、研究FoxG1对内耳干细胞的调控作用及机制；二、在毛细胞损伤模型中研究FoxG1对毛细胞再生的作用及机制；三、研究FoxG1与Notch信号的协同作用对内耳干细胞的调控作用；四、在毛细胞损伤模型中研究两种信号通路的协同作用对毛细胞再生的作用。本项目将为临床上应用内耳干细胞再生毛细胞从而恢复听觉功能奠定理论和实验基础。

Sensorineural deafness is caused by loss of cochlear hair cells. Cochlear Lgr5+ cells are inner ear stem cells, and inhibition of Notch signaling can promote hair cell regeneration. However, regulation of Notch signaling alone not so significantly promote hair cell regeneration. The important transcription factor FoxG1 regulates the proliferation and differentiation of neural stem cells, and can interact with the key factors of the Notch signaling pathway to regulate the downstream genes. However, the role of FoxG1 in regulating the inner ear stem cells remains uninvestigated. This project has been designed to investigate the role of FoxG1 in hair cell regeneration; with the goal to promote the regeneration of hair cells from inner ear stem cells by co-regulation of FoxG1 and Notch signaling pathway. In this project we propose to fulfill the following aims: 1) investigate the role of FoxG1 in regulating the inner ear stem cells; 2) in hair cell damage model, investigate the role of FoxG1 in regulating hair cell regeneration; 3) investigate the co-regulation of FoxG1 and Notch signaling pathway on the inner ear stem cells; 4) in hair cell damage model, investigate the co-regulation of FoxG1 and Notch signaling pathway on hair cell regeneration. The goal of this study is to establish the theoretical and experimental foundation for the clinical treatment of sensorineural hearing loss by stem cell therapy.