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

Garrett A Soukup; Bernd Fritzsch; Marsha L Pierce; Michael D Weston; Israt Jahan; Michael T McManus; Brian D Harfe

doi:10.1016/j.ydbio.2009.01.037

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

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

Garrett A Soukup, Bernd Fritzsch, Marsha L Pierce, Michael D Weston, Israt Jahan, Michael T McManus and Brian D Harfe

Developmental biology, Vol.328(2), pp.328-341

04/15/2009

DOI: 10.1016/j.ydbio.2009.01.037

PMCID: PMC2793102

PMID: 19389351

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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.

Floxed Dicer

RNA interference

MicroRNA

Hair cell

Inner ear development

Conditional knockout

Sensory epithelium

Details

Title: Subtitle: Residual microRNA expression dictates the extent of inner ear development in conditional Dicer knockout mice
Creators: Garrett A Soukup - Department of Biomedical Sciences, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178, USA
Bernd Fritzsch - Department of Biology, University of Iowa, 143 Biology Building, Iowa City, IA 52242, USA
Marsha L Pierce - Department of Biomedical Sciences, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178, USA
Michael D Weston - Department of Biomedical Sciences, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178, USA
Israt Jahan - Department of Biology, University of Iowa, 143 Biology Building, Iowa City, IA 52242, USA
Michael T McManus - Department of Microbiology and Immunology Diabetes Center, University of California, 513 Parnassus Avenue, San Francisco, CA 94143, USA
Brian D Harfe - Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, 1600 SW Archer Road, Gainesville, FL 32610, USA
Resource Type: Journal article
Publication Details: Developmental biology, Vol.328(2), pp.328-341
DOI: 10.1016/j.ydbio.2009.01.037
PMID: 19389351
PMCID: PMC2793102
NLM abbreviation: Dev Biol
ISSN: 0012-1606
eISSN: 1095-564X
Publisher: Elsevier Inc
Language: English
Date published: 04/15/2009
Academic Unit: Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984070700302771

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