Wnt和Fgf信号通路在斑马鱼神经丘毛细胞再生中的相互作用及机制研究

感音神经性聋的治疗目前仍是难题，促进受损的内耳毛细胞再生是重要的解决途径。支持细胞增殖和毛细胞转分化是毛细胞再生中的基本生物学行为，对细胞增殖和分化的调控成为促进毛细胞损伤后再生的关键。有研究报道Wnt信号通路能有效促进支持细胞的增殖，Fgf信号通路与毛细胞分化相关。我们前期研究观察到Wnt和Fgf信号通路均参与毛细胞再生进程，然而Fgf信号通路在斑马鱼毛细胞再生中的作用和分子机制目前并不清楚，Wnt和Fgf信号通路在毛细胞再生中是否有相互作用目前也未有报道。这些均是了解毛细胞再生机制的关键问题。在本课题研究中，我们将以斑马鱼侧线器神经丘毛细胞为研究对象，明确Wnt和Fgf信号通路在毛细胞再生中的具体作用和机制，进一步通过异位显性试验研究两者之间的相互作用，同时，通过原位杂交和RNA-Seq试验探索其相互作用的分子机制和靶点，并最终为哺乳动物内耳毛细胞再生提供新的思路和理论依据。

The treatment of sensorineural hearing loss is still difficult and the promotion of damaged inner ear hair cell (HC) regeneration is an important solution. Supporting cell (SC) proliferation and hair cell transdifferentiation are the basic biological behaviors in HC regeneration. Thus, regulation of cell proliferation and differentiation becomes the key to promote regeneration after HC damage. Several studies have reported that Wnt signaling pathway can effectively induce the proliferation of SCs, while Fgf signaling pathway plays important role in HC differentiation. Our previous study observed that Wnt and Fgf signaling pathways were both involved in the process of HC regeneration. However, little is known about the role and mechanisms of Fgf signaling pathway in zebrafish HC regeneration, and the crosstalk between Wnt and Fgf signaling pathway during the process of HC regeneration remains undiscovered. These are all key issues for understanding the mechanisms of HC regeneration. In this study, we use zebrafish lateral line neuromast as experimental model to study the specific role of Wnt and Fgf signaling pathway in HC regeneration, and to further verify their interactions through epistasis experiments. At the same time, the molecular mechanisms and target point of their crosstalk will be explored by in situ hybridization and RNA-Seq assays, which finally provide new ideas and theoretical basis for HC regeneration of mammalian inner ear.