Cited by 114Hearing, Cochlea, Tinnitus, GeneticsCongenital Ear and Nasal AnomaliesHearing Loss and Rehabilitation

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miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells

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Kuhn, Stephanie, Johnson, Stuart L., Furness, David N., Chen, Jing, Ingham, Neil, Hilton, Jennifer M., Steffes, Georg, Lewis, Morag A., Zampini, Valeria, Hackney, Carole M., Masetto, Sergio, Holley, Matthew C., Steel, Karen P., Marcotti, Walter·2011·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1016646108PMC PMC3038748

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Abstract

MicroRNAs (miRNAs) are small noncoding RNAs able to regulate a broad range of protein-coding genes involved in many biological processes. miR-96 is a sensory organ-specific miRNA expressed in the mammalian cochlea during development. Mutations in miR-96 cause nonsyndromic progressive hearing loss in humans and mice. The mouse mutant diminuendo has a single base change in the seed region of the Mir96 gene leading to widespread changes in the expression of many genes. We have used this mutant to explore the role of miR-96 in the maturation of the auditory organ. We found that the physiological development of mutant sensory hair cells is arrested at around the day of birth, before their biophysical differentiation into inner and outer hair cells. Moreover, maturation of the hair cell stereocilia bundle and remodelling of auditory nerve connections within the cochlea fail to occur in miR-96 mutants. We conclude that miR-96 regulates the progression of the physiological and morphological differentiation of cochlear hair cells and, as such, coordinates one of the most distinctive functional refinements of the mammalian auditory system.

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Authors: Kuhn, S., Johnson, S. L., Furness, D. N., Chen, J., Ingham, N., Hilton, J. M., Steffes, G., Lewis, M. A., Zampini, V., Hackney, C. M., Masetto, S., Holley, M. C., Steel, K. P., & Marcotti, W.
Affiliations: University of Sheffield (GB)
Keele University (GB)
Wellcome Sanger Institute (GB)
University of Pavia (IT)
ORCID: Johnson, Stuart L.
Furness, David N.
Chen, Jing
Ingham, Neil
Lewis, Morag A.
Zampini, Valeria
Masetto, Sergio
Holley, Matthew C.
Steel, Karen P.
Marcotti, Walter
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2011-01-18
Volume: 108
Issue: 6
Pages: 2355-2360
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1016646108
PMC: PMC3038748
OpenAlex: W2027444951
Cited by: 114
References: 51
Citations by year: 2026: 3 · 2025: 8 · 2024: 10 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 7 · 2019: 4 · 2018: 8 · 2017: 9 · 2016: 7 · 2015: 6 · 2014: 6 · 2013: 14 · 2012: 15
FWCI: 7.24
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Research Portal (King's College London) (submittedVersion)
Funders: Wellcome Trust (077189, 088719)
Deafness Research UK
Henry Smith Charity
University of Sheffield
Medical Research Council (MC_qA137918)
Topics: Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
Health Sciences › Medicine › Genetics (clinical) › Congenital Ear and Nasal Anomalies
Health Sciences › Health Professions › Speech and Hearing › Hearing Loss and Rehabilitation
Keywords: miR-96, microRNA, cochlear hair cells, inner hair cells, outer hair cells, hair cell differentiation, progressive hearing loss
MeSH terms: Animals, Cell Differentiation, Hair Cells, Auditory, Inner, Mice, Mutant Strains, Mutation, Organ Specificity, Hair Cells, Auditory, Outer, MicroRNAs, Mice

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miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells

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