Sonic Hedgehog信号通路与内耳发育调控

doi:10.3724/SP.J.1005.2013.01058

遗传 ›› 2013, Vol. 35 ›› Issue (9): 1058-1064.doi: 10.3724/SP.J.1005.2013.01058

Sonic Hedgehog信号通路与内耳发育调控

陈志强¹, 韩新焕², 曹新²

1. 南京医科大学第一临床医学院, 南京 210029; 2. 南京医科大学基础医学院, 南京 210029

收稿日期:2013-04-22 修回日期:2013-06-24 出版日期:2013-09-20 发布日期:2013-09-25
通讯作者: 曹新 E-mail:caoxin@njmu.edu.cn
基金资助:
国家级大学生创新创业训练计划项目(编号：201210312014), 江苏省高等学校大学生实践创新训练计划项目(重点)(编号：2012JSSPITP1025)和江苏高校优势学科建设工程项目资助

Sonic Hedgehog signaling pathway and regulation of inner ear de-velopment

CHEN Zhi-Qiang¹, HAN Xin-Huan², CAO Xin²

1. The First Clinical Medical College, Nanjing Medical University, Nanjing 210029, China; 2. School of Basic Medicine, Nanjing Medical University, Nanjing 210029, China

Received:2013-04-22 Revised:2013-06-24 Online:2013-09-20 Published:2013-09-25

摘要/Abstract

摘要：

在内耳发育过程中, Sonic Hedgehog(Shh)信号通路参与确定了内耳的腹侧极性、螺旋神经元的诱导及毛细胞发育。Shh由菱脑底端分泌, 与顶端产生的Wnt相互拮抗, 共同调节内耳的背腹轴形成。Shh作为神经元细胞的促分裂因子, 能够直接促进螺旋神经元细胞的发育。Shh信号的激活可导致Tbx1对Ngn1的抑制减弱, 间接上调了Ngn1的表达, 调控内耳的神经形成过程。通过调节耳蜗前体细胞的细胞周期, Shh通路参与了内耳毛细胞的分化过程。Shh从蜗管底部至顶部的浓度逐渐降低保证了毛细胞的正常发育顺序。动物实验及对听力障碍患者的研究均表明, Shh通路的传导缺陷将影响靶基因的转录, 进而干扰内耳的正常发育, 引起听力障碍。人类异常Shh信号所致听力障碍的疾病包括Greig cephalopolysyndactyly syndrome (GCPS)、Pallister-Hall syndrome (PHS)、Waardenburg syndrome (WS)及髓母细胞瘤等。文章总结了Shh信号通路在内耳发育调控领域的最新研究进展, 为内耳发育的分子生物学机制及临床应用奠定了理论基础。

关键词: 内耳, Sonic Hedgehog信号通路, 发育, 听力障碍

Abstract:

During inner ear development, Sonic Hedgehog (Shh) signaling pathway is involved in the ventral otic identity, cell fate determination of statoacoustic ganglion neurons and hair cell development. Shh protein, secreted from floor plate, antagonizes Wnt protein from roof plate, which refines and maintains dorsoventral axial patterning in the ear. Shh, served as a mitogen during neurogenesis, directly promotes the development of spiral ganglion neuron. After Shh signaling pathway is activated, Ngn1 is freed from Tbx1 repression. As a result, Shh indirectly upregulates the expression of Ngn1, thus regulating neurogenic patterning of inner ear. In addition, Shh regulates the differentiation of hair cells by influencing cell cycle of the progenitor cells located in the cochlea. The basal-to-apical wave of Shh decline ensures the normal devel-opment pattern of hair cells. It is confirmed by a quantity of researches conducted in both animals and patients with heredi-tary hearing impairment that abnormal Shh signaling results in aberrant transcription of target genes, disturbance of the proper development of inner ear, and human hearing impairment. In humans, diseases accompanied by hearing disorders caused by abnormal Shh signaling include Greig cephalopolysyndactyly syndrome (GCPS), Pallister-Hall syndrome (PHS), Waardenburg syndrome (WS) and medulloblastoma, etc. This review would provide a theoretical basis for further study of molecular mechanisms and clinical use of inner ear development.

Key words: Sonic Hedgehog signaling, development, inner ear, hearing impairment

陈志强韩新焕曹新. Sonic Hedgehog信号通路与内耳发育调控[J]. 遗传, 2013, 35(9): 1058-1064.

CHEN Zhi-Qiang HAN Xin-Huan CAO Xin. Sonic Hedgehog signaling pathway and regulation of inner ear de-velopment[J]. HEREDITAS, 2013, 35(9): 1058-1064.

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