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MicroRNA-183 Family Members Regulate Sensorineural Fates in the Inner Ear
Open accessAbstract
Members of the microRNA (miRNA) 183 family (miR-183, miR-96, and miR-182) are expressed abundantly in specific sensory cell types in the eye, nose, and inner ear. In the inner ear, expression is robust in the mechanosensory hair cells and weak in the associated statoacoustic ganglion (SAG) neurons; both cell types can share a common lineage during development. Recently, dominant-progressive hearing loss in humans and mice was linked to mutations in the seed region of miR-96, with associated defects in both development and maintenance of hair cells in the mutant mice. To understand how the entire triplet functions in the development of mechanosensory hair cells and neurons of the inner ear, we manipulated the levels of these miRNAs in zebrafish embryos using synthesized miRNAs and antisense morpholino oligonucleotides (MOs). Overexpression of miR-96 or miR-182 induces duplicated otocysts, ectopic or expanded sensory patches, and extra hair cells, whereas morphogenesis of the SAG is adversely affected to different degrees. In contrast, knockdown of miR-183, miR-96, and miR-182 causes reduced numbers of hair cells in the inner ear, smaller SAGs, defects in semicircular canals, and abnormal neuromasts on the posterior lateral line. However, the prosensory region of the posterior macula, where the number of hair cells is reduced by ∼50%, is not significantly impaired. Our findings suggest both distinct and common roles for the three miRNAs in cell-fate determination in the inner ear, and these principles might apply to development of other sensory organs.
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“Importantly, this highly conserved family of miRNAs shows expression in ciliated neurosensory organs across phyla and has recently been demonstrated to contribute specifically to the differentiation and function of the mechanosensory hair cells in the vertebrate inner ear (10,11).”
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 [11]
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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 [11]
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Metadata
- Authors
- Li, H., Kloosterman, W., & Fekete, D. M.
- Affiliations
- Purdue University West Lafayette (US)
- University Medical Center Utrecht (NL)
- Corresponding author
- Fekete, Donna M.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-03-03
- Volume
- 30
- Issue
- 9
- Pages
- 3254-3263
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2848753
- OpenAlex
- W1986214497
- Cited by
- 140
- References
- 39
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 9 · 2018: 9 · 2017: 17 · 2016: 11 · 2015: 8 · 2014: 6 · 2013: 14 · 2012: 13
- FWCI
- 7.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Deafness and Other Communication Disorders (R21DC008997)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Genetics (clinical) › Congenital Ear and Nasal Anomalies
- Keywords
- miR-183, miR-96, miR-182, inner ear development, mechanosensory hair cells, cell fate determination, zebrafish, morpholino knockdown, otocyst, semicircular canals, neuromasts, lateral line
- MeSH terms
- Animals, Cell Count, Cochlear Nerve, Hair Cells, Auditory, Ear, Inner, Mutation, Nervous System Malformations, Sensory Receptor Cells, Spiral Ganglion, Zebrafish, Down-Regulation, Oligonucleotides, Antisense, Gene Expression Regulation, Developmental, Cell Lineage, Body Patterning, MicroRNAs, Cell Proliferation, Lateral Line System, Gene Knockdown Techniques
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