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Cited by 125Hearing, Cochlea, Tinnitus, GeneticsCongenital Ear and Nasal AnomaliesDevelopmental Biology and Gene Regulation

Residual microRNA expression dictates the extent of inner ear development in conditional Dicer knockout mice

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Soukup, Garrett A., Fritzsch, Bernd, Pierce, Marsha L., Weston, Michael D., Jahan, Israt, McManus, Michael T., Harfe, Brian D.·2009·Developmental Biology
DOI 10.1016/j.ydbio.2009.01.037PMC PMC2793102
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Abstract

Inner ear development requires coordinated transformation of a uniform sheet of cells into a labyrinth with multiple cell types. While numerous regulatory proteins have been shown to play critical roles in this process, the regulatory functions of microRNAs (miRNAs) have not been explored. To demonstrate the importance of miRNAs in inner ear development, we generated conditional Dicer knockout mice by the expression of Cre recombinase in the otic placode at E8.5. Otocyst-derived ganglia exhibit rapid neuron-specific miR-124 depletion by E11.5, degeneration by E12.5, and profound defects in subsequent sensory epithelial innervations by E17.5. However, the small and malformed inner ear at E17.5 exhibits residual and graded hair cell-specific miR-183 expression in the three remaining sensory epithelia (posterior crista, utricle, and cochlea) that closely corresponds to the degree of hair cell and sensory epithelium differentiation, and Fgf10 expression required for morphohistogenesis. The highest miR-183 expression is observed in near-normal hair cells of the posterior crista, whereas the reduced utricular macula demonstrates weak miR-183 expression and develops presumptive hair cells with numerous disorganized microvilli instead of ordered stereocilia. The correlation of differential and delayed depletion of mature miRNAs with the derailment of inner ear development demonstrates that miRNAs are crucial for inner ear neurosensory development and neurosensory-dependent morphogenesis.

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  • The miR-96, miR-182 and miR-183 miRNA family is essential for differentiation and function of the vertebrate inner ear.

    “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 [10]

    The Abstract reports that residual miR-183 expression closely corresponds to the degree of hair-cell differentiation, and the Discussion (‘Hair cell development’; page unavailable) describes a critical role for miRNAs in that process. But this Dicer-knockout study does not establish that the miR-96/182/183 family specifically is essential, or demonstrate its role in hair-cell function. (LLM, conf=0.88)

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Authors
Soukup, G. A., Fritzsch, B., Pierce, M. L., Weston, M. D., Jahan, I., McManus, M. T., & Harfe, B. D.
Affiliations
  • Creighton University (US)
  • University of Iowa (US)
  • University of California, San Francisco (US)
  • University of Florida (US)
Corresponding author
Soukup, Garrett A.
ORCID
Venue
Developmental Biology
Publisher
Elsevier BV
Published
2009-04
Volume
328
Issue
2
Pages
328-341
ISSN
0012-1606 (ISSN-L)
DOI
10.1016/j.ydbio.2009.01.037
PMC
PMC2793102
OpenAlex
W1987096821
Cited by
125
References
2
Citations by year
2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 6 · 2019: 3 · 2018: 8 · 2017: 8 · 2016: 7 · 2015: 2 · 2014: 8 · 2013: 13 · 2012: 22
FWCI
9.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation
  • National Institutes of Health (5p20rr018788-07)
  • U.S. Public Health Service
  • National Institute on Deafness and Other Communication Disorders (R01DC009025, R01DC005590)
  • National Center for Research Resources (#P20 RR018788, C06RR017417)
  • Office of Experimental Program to Stimulate Competitive Research
Topics
  • Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
  • Health Sciences › Medicine › Genetics › Congenital Ear and Nasal Anomalies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
microRNA, inner ear development, Dicer, conditional knockout mice, miR-124, miR-183, otic placode, hair cell differentiation, sensory epithelia, FGF10, cochlea, utricle, stereocilia
MeSH terms
Animals, Cell Differentiation, Cochlea, Endoribonucleases, Epithelium, Hair Cells, Auditory, Ear, Inner, Mice, Knockout, MicroRNAs, Organogenesis, Ribonuclease III, Mice, Fibroblast Growth Factor 10, DEAD-box RNA Helicases

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