遗传 ›› 2018, Vol. 40 ›› Issue (7): 515-524.doi: 10.16288/j.yczz.17-407

• 综述 •    下一篇

FGF信号通路在内耳发育调控和毛细胞再生中的作用

杨志1,姚俊2(),曹新2   

  1. 1. 南京医科大学第一临床医学院,南京 211166
    2. 南京医科大学生物技术系,南京 211166
  • 收稿日期:2018-03-21 修回日期:2018-05-08 出版日期:2018-07-20 发布日期:2018-05-23
  • 作者简介:杨志,本硕连读生,专业方向:临床医学。E-mail:yang_zhi1209@126.com
  • 基金资助:
    中国博士后科学基金项目(2016M600431);江苏省博士后科研资助项目(1601071B)

Roles of the FGF signaling pathway in regulating inner ear development and hair cell regeneration

Yang Zhi1,Yao Jun2(),Cao Xin2   

  1. 1. The First Clinical Medical College, Nanjing Medical University, Nanjing 211166, China
    2. Department of Biotechnology, Nanjing Medical University, Nanjing 211166, China
  • Received:2018-03-21 Revised:2018-05-08 Online:2018-07-20 Published:2018-05-23
  • Supported by:
    Surpported by China Postdoctoral Science Foundation(2016M600431);Jiangsu Planned Projects for Postdoctoral Research Funds(1601071B)

摘要:

内耳是感受听觉和平衡觉的复杂器官。在内耳发育过程中,成纤维生长因子(fibroblast growth factor, FGF)信号通路参与了听基板的诱导、螺旋神经节(statoacoustic ganglion, SAG)的发育以及Corti器感觉上皮的分化。FGF信号开启了内耳早期发育的基因调控网络,诱导前基板区域以及听基板的形成。正常表达的FGF信号分子可促进听囊腹侧成神经细胞的特化,但成熟SAG神经元释放的过量FGF5可抑制此过程,形成负反馈环路使SAG在稳定状态下发育。FGF20在Notch信号通路的调控下参与了前感觉上皮区域向毛细胞和支持细胞的分化过程,而内毛细胞分泌的FGF8可调控局部支持细胞分化为柱细胞。人类FGF信号通路异常可导致多种耳聋相关遗传病。此外,FGF信号通路在低等脊椎动物毛细胞自发再生以及干细胞向内耳毛细胞诱导过程中都起到了关键作用。本文综述了FGF信号通路在内耳发育调控以及毛细胞再生中的作用及其相关研究进展,以期为毛细胞再生中FGF信号通路调控机制的阐明奠定理论基础。

关键词: FGF信号通路, 内耳, 发育, 毛细胞, 再生

Abstract:

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.

Key words: FGF signaling pathway, inner ear, development, hair cell, regeneration