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miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells
Open accessAbstract
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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“Recently, point mutations within the seed region of miR-96 were reported in two Spanish families with autosomal dominant non-syndromic sensorineural hearing loss (NSHL) and in a mouse model of NSHL.”
From A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing (2012) · cites this paper as [16]
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“Indeed, tight regulation of miR-96 levels within the vertebrate inner ear seems to be crucial for the correct function and development of hair cells, as demonstrated by knockdown experiments in zebrafish (11) and by the phenotypic differences between the heterozygous and the homozygous diminuendo mice (15,16).”
From A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing (2012) · cites this paper as [16]
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Metadata
- 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
- 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
- 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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