Yang Zhi, Yao Jun, Cao Xin
The First Clinical Medical College, Nanjing Medical University, Nanjing 211166, China.
Department of Biotechnology, Nanjing Medical University, Nanjing 211166, China.
Yi Chuan. 2018 Jul 20;40(7):515-524. doi: 10.16288/j.yczz.17-407.
The inner ear is a complex sensory organ that detects sound and mediates balance. During inner ear development, fibroblast growth factor (FGF) signaling pathway is involved in the induction of otic placode, cell fate determination of statoacoustic ganglion (SAG) neurons, and epithelial differentiation of the Corti organ. FGF signaling initiates the regulatory network of otic genes in the early development of inner ear, and induces the formation of pre-placodal region and the otic placode. The specification of the neuroblast ventral to the otic vesicle could be promoted by the normally-expressed FGF, and inhibited by excessive FGF5 secreted by mature SAG neurons, which could form a negative feedback loop and stabilize the SAG cell identity. The expression of FGF20 is regulated by the Notch signaling pathway and implicated in the differentiation of hair cells and supporting cells in the prosensory epithelium. FGF8 secreted by hair cells could regulate the differentiation of partial supporting cells into pillar cells. Abnormal FGF signaling in humans could lead to different kinds of deafness-related genetic diseases. In addition, it is noteworthy that FGF signaling pathway plays an important role in hair cell regeneration and induction from stem cells in lower vertebrates. In this review, we summarize recent advancements on roles of the FGF signaling pathway in inner ear development and hair cell regeneration, and lay a theoretical foundation for elucidating the regulatory mechanisms of FGF signal pathway in hair cell regeneration.
内耳是一个复杂的感觉器官，可检测声音并调节平衡。在内耳发育过程中，成纤维细胞生长因子（FGF）信号通路参与耳基板的诱导、 statoacoustic神经节（SAG）神经元的细胞命运决定以及柯蒂氏器的上皮分化。FGF信号在内耳早期发育中启动耳基因的调控网络，并诱导前基板区域和耳基板的形成。耳泡腹侧神经母细胞的特化可由正常表达的FGF促进，并由成熟SAG神经元分泌的过量FGF5抑制，这可形成负反馈回路并稳定SAG细胞身份。FGF20的表达受Notch信号通路调控，并与前感觉上皮中毛细胞和支持细胞的分化有关。毛细胞分泌的FGF8可调节部分支持细胞向柱细胞的分化。人类FGF信号异常可导致不同类型的耳聋相关遗传病。此外，值得注意的是，FGF信号通路在低等脊椎动物的毛细胞再生和干细胞诱导中起重要作用。在本综述中，我们总结了FGF信号通路在内耳发育和毛细胞再生中的作用的最新进展，为阐明FGF信号通路在毛细胞再生中的调控机制奠定了理论基础。
