Atoh1 regulation in the cochlea: more than just transcription
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More than 80% of all cases of deafness are related to the death or degeneration of cochlear hair cells and the associated spiral ganglion neurons, and a lack of regeneration of these cells leads to permanent hearing loss. Therefore, the regeneration of lost hair cells is an important goal for the treatment of deafness. Atoh1 is a basic helix-loop-helix (bHLH) transcription factor that is critical in both the development and regeneration of cochlear hair cells. Atoh1 is transcriptionally regulated by several signaling pathways, including Notch and Wnt signalings. At the post-translational level, it is regulated through the ubiquitin-proteasome pathway. In vitro and in vivo studies have revealed that manipulation of these signaling pathways not only controls development, but also leads to the regeneration of cochlear hair cells after damage. Recent progress toward understanding the signaling networks involved in hair cell development and regeneration has led to the development of new strategies to replace lost hair cells. This review focuses on our current understanding of the signaling pathways that regulate Atoh1 in the cochlea.
Key wordsAtoh1 Huwe1 Cochlea Hair cells Regeneration Post-translational regulation
Atoh1 属于bHLH 转录因子家族成员,其对耳蜗 毛细胞的胚胎发育及损伤后再生具有重要作用。 许多讯号通道在转录水平上对Atoh1 有调节作 用,包括Notch 和Wnt 通道。在蛋白转译后水平, Atoh1 是经由泛素-蛋白酶通道所调节。体外细胞 实验及体内动物实验都显示:经由上述讯号通道 的调节手段不仅影响耳蜗发育,也导致毛细胞的 损伤后再生。本综述回顾了耳蜗内各个对Atoh1 调节讯号通道研究的进展,并聚焦于泛素-蛋白 酶通道对Atoh1 进行转译后调节及其对毛细胞发 育的影响。
关键词Atoh1 Huwe1 耳蜗 毛细胞 再生 转译后调节
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- Davis, A.C., 1983. Hearing disorders in the population: first phase findings of the MRC national study of hearing. In: Lutman, M.E., Haggard, M.P. (Eds.), Hearing Science and Hearing Disorders. Academic Press Inc. (London) Ltd., London, p.35–60. https://doi.org/10.1016/B978-0-12-460440-7.50007-7CrossRefGoogle Scholar
- Incesulu, A., Nadol, J.B., 1998. Correlation of acoustic threshold measures and spiral ganglion cell survival in severe to profound sensorineural hearing loss: implications for cochlear implantation. Ann. Otol. Rhinol. Laryngol., 107(11): 906–911. https://doi.org/10.1177/000348949810701102PubMedCrossRefGoogle Scholar
- Pan, N., Jahan, I., Kersigo, J., et al., 2012. A novel Atoh1 “self-terminating” mouse model reveals the necessity of proper Atoh1 level and duration for hair cell differentiation and viability. PLoS ONE, 7(1): e30358. https://doi.org/10.1371/journal.pone.0030358PubMedPubMedCentralCrossRefGoogle Scholar
- Rose, M.F., Ahmad, K.A., Thaller, C., et al., 2009. Excitatory neurons of the proprioceptive, interoceptive, and arousal hindbrain networks share a developmental requirement for math1. Proc. Natl. Acad. Sci. USA, 106(52): 22462–22467. https://doi.org/10.1073/pnas.0911579106PubMedPubMedCentralCrossRefGoogle Scholar
- WHO (World Health Organization), 2017. Deafness and hearing loss. Fact sheet, WHO Media Centre.Google Scholar
- Zhao, X., D'Arca, D., Lim, W.K., et al., 2009. The N-Myc-DLL3 cascade is suppressed by the ubiquitin ligase Huwe1 to inhibit proliferation and promote neurogenesis in the developing brain. Dev. Cell, 17(2): 210–221. https://doi.org/10.1016/j.devcel.2009.07.009PubMedPubMedCentralCrossRefGoogle Scholar