Genetic and Pharmacologic Alterations of Claudin9 Levels Suffice to Induce Functional and Mature Inner Hair Cells

Overview

Journal bioRxiv

Date 2023 Oct 24

PMID 37873357

Authors

Yingying Chen

Jeong Han Lee

Jin Li

Seojin Park

Maria C Perez Flores

Braulio Peguero

Jennifer Kersigo

Mincheol Kang

Jinsil Choi

Lauren Levine

Michael Anne Gratton

Bernd Fritzsch

Ebenezer N Yamoah

Affiliations

Soon will be listed here.

Abstract

Hearing loss is the most common form of sensory deficit. It occurs predominantly due to hair cell (HC) loss. Mammalian HCs are terminally differentiated by birth, making HC loss challenging to replace. Here, we show the pharmacogenetic downregulation of , a tight junction protein, generates robust supernumerary inner HCs (IHCs) in mice. The ectopic IHC shared functional and synaptic features akin to typical IHCs and were surprisingly and remarkably preserved for at least fifteen months >50% of the mouse's life cycle. , knockdown using shRNA on postnatal days (P) P2-7 yielded analogous functional ectopic IHCs that were equally durably conserved. The findings suggest that Cldn9 levels coordinate embryonic and postnatal HC differentiation, making it a viable target for altering IHC development pre- and post-terminal differentiation.

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