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

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

Research output: Contribution to journalArticle

91 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)328-341
Number of pages14
JournalDevelopmental Biology
Volume328
Issue number2
DOIs
StatePublished - Apr 15 2009

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Inner Ear
MicroRNAs
Knockout Mice
Epithelium
Stereocilia
Saccule and Utricle
Cochlea
Microvilli
Morphogenesis
Ganglia
Ear
Neurons
Proteins

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Cite this

Residual microRNA expression dictates the extent of inner ear development in conditional Dicer knockout mice. / Soukup, Garrett; Fritzsch, Bernd; Pierce, Marsha L.; Weston, Michael; Jahan, Israt; McManus, Michael T.; Harfe, Brian D.

In: Developmental Biology, Vol. 328, No. 2, 15.04.2009, p. 328-341.

Research output: Contribution to journalArticle

Soukup, Garrett ; Fritzsch, Bernd ; Pierce, Marsha L. ; Weston, Michael ; Jahan, Israt ; McManus, Michael T. ; Harfe, Brian D. / Residual microRNA expression dictates the extent of inner ear development in conditional Dicer knockout mice. In: Developmental Biology. 2009 ; Vol. 328, No. 2. pp. 328-341.
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