CASZ1 regulates the rate at which outer hair cells mature and is required for hearing

Yoko Nakano; Elizabeth C. Driver; Susan C. Wiechert; Braulio Peguero; Erich T. Boger; Chantal Allamargot; Rebecca Hipp; Angelika Doetzlhofer; Robert J. Morell; Matthew W. Kelley; Botond Bánfi

doi:10.1101/2025.07.04.663233

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CASZ1 regulates the rate at which outer hair cells mature and is required for hearing

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CASZ1 regulates the rate at which outer hair cells mature and is required for hearing

Yoko Nakano, Elizabeth C. Driver, Susan C. Wiechert, Braulio Peguero, Erich T. Boger, Chantal Allamargot, Rebecca Hipp, Angelika Doetzlhofer, Robert J. Morell, Matthew W. Kelley, …

bioRxiv

Cold Spring Harbor Laboratory, 1.1

07/05/2025

DOI: 10.1101/2025.07.04.663233

PMCID: PMC12236522

PMID: 40631138

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https://doi.org/10.1101/2025.07.04.663233View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

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 stereocilia bundles in OHCs; abnormally low F-actin density in OHC cuticular plates; 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.

Developmental Biology

Details

Title: Subtitle: CASZ1 regulates the rate at which outer hair cells mature and is required for hearing
Creators: Yoko Nakano - University of Iowa
Elizabeth C. Driver - National Institute on Deafness and Other Communication Disorders
Susan C. Wiechert - University of Iowa
Braulio Peguero - National Institute on Deafness and Other Communication Disorders
Erich T. Boger - National Institute on Deafness and Other Communication Disorders
Chantal Allamargot - Central Microscopy Research Facility, University of Iowa
Rebecca Hipp - National Institute on Deafness and Other Communication Disorders
Angelika Doetzlhofer - Johns Hopkins University School of Medicine
Robert J. Morell - National Institute on Deafness and Other Communication Disorders
Matthew W. Kelley - National Institute on Deafness and Other Communication Disorders
Botond Bánfi - Department of Internal Medicine, Carver College of Medicine, University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
Edition: 1.1
DOI: 10.1101/2025.07.04.663233
PMID: 40631138
PMCID: PMC12236522
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory
Number of pages: 47
Language: English
Date posted: 07/05/2025
Academic Unit: Anatomy and Cell Biology; Core Research Facilities; Otolaryngology; Internal Medicine
Record Identifier: 9984845652302771

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