Genetic and pharmacologic alterations of claudin9 levels suffice to induce functional and mature inner hair cells

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

doi:10.1101/2023.10.08.561387

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Genetic and pharmacologic alterations of claudin9 levels suffice to induce functional and mature inner hair cells

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Genetic and pharmacologic alterations of claudin9 levels suffice to induce functional and mature inner hair cells

Yingying Chen, Jeong Han Lee, Jin Li, Seojin Park, Maria C. Perez Flores, Braulio Peguero, Jennifer Kersigo, Mincheol Kang, Jinsil Choi, Lauren Levine, …

bioRxiv

Cold Spring Harbor Laboratory

10/10/2023

DOI: 10.1101/2023.10.08.561387

PMCID: PMC10592694

PMID: 37873357

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https://doi.org/10.1101/2023.10.08.561387View

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

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 incurable. Here, we show the pharmacogenetic downregulation of Cldn9, a tight junction protein, generates robust supernumerary inner HCs (IHCs) in mice. The putative ectopic IHCs have 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. In vivo, Cldn9 knockdown using shRNA on postnatal days (P) P1-7 yielded analogous functional putative 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.

Details

Title: Subtitle: Genetic and pharmacologic alterations of claudin9 levels suffice to induce functional and mature inner hair cells
Creators: Yingying Chen - University of Nevada, Reno
Jeong Han Lee - University of Nevada, Reno
Jin Li - University of Washington
Seojin Park - University of Nevada, Reno
Maria C. Perez Flores
Braulio Peguero - University of Nevada, Reno
Jennifer Kersigo - University of Iowa
Mincheol Kang
Jinsil Choi - University of Nevada, Reno
Lauren Levine - Washington University in St. Louis
Michael Anne Gratton - Boys Town National Research Hospital
Bernd Fritzsch
Ebenezer N. Yamoah
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2023.10.08.561387
PMID: 37873357
PMCID: PMC10592694
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 10/10/2023
Academic Unit: Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984500078102771

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