PDF(Pubmed)
Abstract：
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.
摘要：
Atoh1过表达对于哺乳动物听觉和前庭器官的感觉上皮中的毛细胞（HC）再生至关重要。然而,单独的Atoh1过表达不能在哺乳动物内耳中诱导完全成熟和有功能的HC。在目前的研究中,我们通过操纵Atoh1在不同发育阶段的表达来研究Atoh1组成型过表达在天然HC中的作用。我们证明，天然前庭HC中Atoh1的组成型过表达不会影响细胞存活，但会通过干扰HC的亚型分化和发束发育而损害前庭功能。相比之下,Atoh1在耳蜗HC中的过表达阻碍了它们的成熟，最终导致耳蜗HC逐渐丢失和听力功能障碍。我们的研究表明，时间限制的Atoh1表达对于内耳HCs的分化和存活至关重要，这对于通过Atoh1过表达诱导的HC再生策略重建听力和前庭功能至关重要。
