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. 2025 Apr 18;388(6744):eado4930.
doi: 10.1126/science.ado4930. Epub 2025 Apr 18.

Casz1 is required for both inner hair cell fate stabilization and outer hair cell survival

Yuwei Sun  1   2 , Minhui Ren  1   2 , Yu Zhang  3   4 , Shuting Li  1   2 , Zhengnan Luo  1   2 , Suhong Sun  1   2 , Shunji He  1 , Guangqin Wang  1   2 , Di Zhang  1   2 , Suzanne L Mansour  5 , Lei Song  3   4 , Zhiyong Liu  1   2   6
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Casz1 is required for both inner hair cell fate stabilization and outer hair cell survival

Yuwei Sun et al. Science. .

Abstract

Cochlear inner hair cells (IHCs) and outer hair cells (OHCs) require different transcription factors for their cell fate stabilization and survival, which suggests that separate mechanisms are involved. In this study, we found that the transcription factor Casz1 is crucial for early IHC fate consolidation and for OHC survival during mouse development. Loss of Casz1 resulted in transdifferentiation of IHCs into OHCs, without affecting OHC production. However, long-term OHC survival was compromised in Casz1 mutant mice. In addition, the transcription factor Gata3 was down-regulated in Casz1-deleted IHCs, and overexpressing Gata3 partially rescued IHC properties, OHC numbers, and hearing in Casz1-deleted mice. Thus, Casz1 plays critical roles in early IHC fate stabilization and OHC survival and could potentially provide a lead for therapies aimed at regenerating both IHCs and OHCs.

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