| Experiment Id | GSE300215 | Name | CASZ1 regulates the rate at which outer hair cells mature and is required for hearing |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2026-09-29 |
| description | The transcriptional activator ATOH1 is a master regulator of the development of mechanosensory hair-cells (HCs) in the ear. We report that the ATOH1 target gene Casz1 encodes a transcription factor that regulates the rate of outer HC (OHC) maturation by gene repression. Genetic deletion of Casz1 during (but not after) development of the mouse cochlea caused: hearing loss; abnormal organization of mechanosensory stereocilium bundles and abnormally low F-actin density in cuticular plates in OHCs; progressive loss of OHCs; and mild morphological alterations in inner HCs. RNA sequencing revealed that Casz1 deletion delayed downregulation of genes expressed in immature OHCs, including the actin regulator-encoding gene Coro2a, and accelerated upregulation of genes expressed in mature OHCs. Coro2a knockdown restored the density of cuticular plate F-actin in Casz1 mutant OHCs. Our data indicate that CASZ1 regulates transcriptional and morphological maturation of OHCs, and that CASZ1 in maturing HCs is necessary for hearing. A floxed allele of the Casz1 gene was conditionally deleted (Casz1-cKO) in the inner ears of mice carrying a Sox10-Cre transgene. Total RNA was extracted from the organs of Corti of postnatal day 4 Casz1-cKO mice (n=42) and wild-type (Casz1-WT) mice (n=39). The extracted RNA was pooled into 5 samples per genotype (7-9 mice per sample) to obtain sufficiently high RNA concentration for sequencing. The RNA samples were reverse-transcribed, and the resulting cDNA was sequenced. Gene expression differences between the two genotypes were evaluated using EdgeR. |
