Rbm24 maintains survival of cochlear outer hair cells by repressing Insm1

ABSTRACT The inactivation of Rbm24, an RNA-binding protein, results in the degeneration of cochlear outer hair cells (OHCs) during the postnatal period. However, the specific molecular mechanisms underlying this OHC death remain elusive. To address this, we conducted a comprehensive analysis comparing the gene profiles of wild-type OHCs to those lacking Rbm24 ( Rbm24 -/- ) at postnatal day 7 (P7). Our results revealed that the overall differentiation program of OHCs is delayed in the absence of Rbm24. Furthermore, the expression of Insm1, a crucial factor for OHC development that is normally switched off by P2, remains prolonged in Rbm24 -/- OHCs. Interestingly, when Insm1 is overexpressed, it also leads to OHC death. Significantly, the OHC degeneration is much less severe when both Rbm24 and Insm1 are simultaneously inactivated. These findings shed light on the important role of Rbm24 in repressing Insm1 and its impact on OHC differentiation and survival. Our study provides valuable insights into the complex genetic signaling pathways involved in OHC development.