ZBTB20 is Essential for Cochlear Maturation and Hearing in Mice

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2023 Jun 6

PMID 37279265

Authors

Zhifang Xie

Xian-Hua Ma

Qiu-Fang Bai

Jie Tang

Jian-He Sun

Fei Jiang

Wei Guo

Chen-Ma Wang

Rui Yang

Yin-Chuan Wen

Fang-Yuan Wang

Yu-Xia Chen

Hai Zhang

David Z He

Matthew W Kelley

Shiming Yang

Weiping J Zhang

Affiliations

Soon will be listed here.

Abstract

The mammalian cochlear epithelium undergoes substantial remodeling and maturation before the onset of hearing. However, very little is known about the transcriptional network governing cochlear late-stage maturation and particularly the differentiation of its lateral nonsensory region. Here, we establish ZBTB20 as an essential transcription factor required for cochlear terminal differentiation and maturation and hearing. ZBTB20 is abundantly expressed in the developing and mature cochlear nonsensory epithelial cells, with transient expression in immature hair cells and spiral ganglion neurons. Otocyst-specific deletion of causes profound deafness with reduced endolymph potential in mice. The subtypes of cochlear epithelial cells are normally generated, but their postnatal development is arrested in the absence of ZBTB20, as manifested by an immature appearance of the organ of Corti, malformation of tectorial membrane (TM), a flattened spiral prominence (SP), and a lack of identifiable Boettcher cells. Furthermore, these defects are related with a failure in the terminal differentiation of the nonsensory epithelium covering the outer border Claudius cells, outer sulcus root cells, and SP epithelial cells. Transcriptome analysis shows that ZBTB20 regulates genes encoding for TM proteins in the greater epithelial ridge, and those preferentially expressed in root cells and SP epithelium. Our results point to ZBTB20 as an essential regulator for postnatal cochlear maturation and particularly for the terminal differentiation of cochlear lateral nonsensory domain.

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