Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.
Elife. 2024 Mar 14;12:RP90025. doi: 10.7554/eLife.90025.
Mammals harbor a limited number of sound-receptor hair cells (HCs) that cannot be regenerated after damage. Thus, investigating the underlying molecular mechanisms that maintain HC survival is crucial for preventing hearing impairment. Intriguingly, or HCs form initially but then rapidly degenerate, whereas HCs degenerate considerably later. However, the transcriptional cascades involving Pou4f3, Gfi1, and Rbm24 remain undescribed. Here, we demonstrate that expression is completely repressed in HCs but unaltered in HCs, and further that the expression of both POU4F3 and GFI1 is intact in HCs. Moreover, by using in vivo mouse transgenic reporter assays, we identify three enhancers to which POU4F3 binds. Lastly, through in vivo genetic testing of whether Rbm24 restoration alleviates the degeneration of HCs, we show that ectopic Rbm24 alone cannot prevent HCs from degenerating. Collectively, our findings provide new molecular and genetic insights into how HC survival is regulated.
哺乳动物内耳中的毛细胞（HCs）数量有限，受损后不能再生。因此，研究维持 HC 存活的潜在分子机制对于预防听力损伤至关重要。有趣的是，在出生时 HCs 形成但随后迅速退化，而 HCs 则在相当晚的时候退化。然而，涉及 Pou4f3、Gfi1 和 Rbm24 的转录级联仍未被描述。在这里，我们证明在 HCs 中完全抑制了 表达，而在 HCs 中未改变，并且进一步证明 POU4F3 和 GFI1 的表达在 HCs 中是完整的。此外，通过使用体内小鼠转基因报告基因检测，我们鉴定了三个 POU4F3 结合的 增强子。最后，通过体内遗传测试，我们研究了 Rbm24 恢复是否可以减轻 HCs 的退化，结果表明单独过表达 Rbm24 并不能防止 HCs 退化。总的来说，我们的研究结果为 HC 存活是如何受到调控的提供了新的分子和遗传见解。
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