Deciphering the genetic interactions between Pou4f3, Gfi1, and Rbm24 in maintaining mouse cochlear hair cell survival.

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.