Endogenous Sox2 expression is essential for Atoh1-induced hair cell addition and regeneration in the mouse utricle
Brief intro:
- Author: Yu-Tong Yang, Jing-Ying Guo, Jun-Yi Xu, Wei- Su, Ming-Yu Hao, Ting Zhang, Shu-Sheng Gong, Guo-Peng Wang
- Journal: Neuroscience
- Doi: https://www.doi.org/10.1016/j.neuroscience.2026.03.051
- Publication Date: 2026/3/31
Abstract
The limited regenerative capacity of vestibular hair cells (HCs) in mammals is one of the causes of permanent balance disorders. The transcription factor Atoh1 has been identified as a potential candidate for inducing HC regeneration. However, regulation of Atoh1 alone has proven insufficient to achieve functional recovery of the mammalian vestibule. Elucidating the mechanisms underlying Atoh1-induced regeneration may therefore inform strategies to enhance its therapeutic efficacy. Endogenous Sox2 is required for Atoh1-associated HC formation during embryonic development, yet its role in Atoh1 overexpression-induced HC formation after birth remains unclear. In this study, we conditionally knocked down Sox2 while overexpressing Atoh1 in the utricle of neonatal mice or in diphtheria-toxin-injured adult mice. Atoh1 overexpression stimulated supporting cell proliferation and new HC formation in neonates; however, concomitant Sox2 knockdown attenuated the effects. In the diphtheria-toxin-injured adult utricle, Sox2 downregulation similarly weakened Atoh1-induced HC regeneration. These findings demonstrate that endogenous Sox2 expression is essential for Atoh1-induced HC addition and regeneration in the mouse utricle.
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