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Journal of Zhejiang University-SCIENCE B

, Volume 20, Issue 2, pp 146–155 | Cite as

Atoh1 regulation in the cochlea: more than just transcription

  • Yen-Fu ChengEmail author
Review
  • 151 Downloads

Abstract

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 words

Atoh1 Huwe1 Cochlea Hair cells Regeneration Post-translational regulation 

Atoh1 转录因子在耳蜗内的转译后调节

摘 要

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 

CLC number

R764.35 

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Copyright information

© Zhejiang University and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Otology and LaryngologyHarvard Medical SchoolBostonUSA
  2. 2.Eaton-Peabody LaboratoryMassachusetts Eye and Ear InfirmaryBostonUSA
  3. 3.Department of Medical ResearchTaipei Veterans General HospitalTaipeiChina
  4. 4.Department of Otolaryngology-Head and Neck SurgeryTaipei Veterans General HospitalTaipeiChina
  5. 5.School of MedicineYang-Ming UniversityTaipeiChina
  6. 6.Department of Speech Language Pathology and AudiologyTaipei University of Nursing and Health ScienceTaipeiChina

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