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Publication : The proper timing of Atoh1 expression is pivotal for hair cell subtype differentiation and the establishment of inner ear function.

First Author  You D Year  2023
Journal  Cell Mol Life Sci Volume  80
Issue  12 Pages  349
PubMed ID  37930405 Mgi Jnum  J:393625
Mgi Id  MGI:8461040 Doi  10.1007/s00018-023-04947-w
Citation  You D, et al. (2023) The proper timing of Atoh1 expression is pivotal for hair cell subtype differentiation and the establishment of inner ear function. Cell Mol Life Sci 80(12):349
abstractText  Atoh1 overexpression is essential for hair cell (HC) regeneration in the sensory epithelium of mammalian auditory and vestibular organs. However, Atoh1 overexpression alone cannot induce fully mature and functional HCs in the mammalian inner ear. In the current study, we investigated the effect of Atoh1 constitutive overexpression in native HCs by manipulating Atoh1 expression at different developmental stages. We demonstrated that constitutive overexpression of Atoh1 in native vestibular HCs did not affect cell survival but did impair vestibular function by interfering with the subtype differentiation of HCs and hair bundle development. In contrast, Atoh1 overexpression in cochlear HCs impeded their maturation, eventually leading to gradual HC loss in the cochlea and hearing dysfunction. Our study suggests that time-restricted Atoh1 expression is essential for the differentiation and survival of HCs in the inner ear, and this is pivotal for both hearing and vestibular function re-establishment through Atoh1 overexpression-induced HC regeneration strategies.
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