MicroRNAs are essential for development and function of inner ear hair cells in vertebrates

Proc Natl Acad Sci U S A. 2009 May 12;106(19):7915-20. doi: 10.1073/pnas.0812446106. Epub 2009 Apr 28.

Abstract

MicroRNAs (miRNAs) inhibit the translation of target mRNAs and affect, directly or indirectly, the expression of a large portion of the protein-coding genes. This study focuses on miRNAs that are expressed in the mouse cochlea and vestibule, the 2 inner ear compartments. A conditional knock-out mouse for Dicer1 demonstrated that miRNAs are crucial for postnatal survival of functional hair cells of the inner ear. We identified miRNAs that have a role in the vertebrate developing inner ear by combining miRNA transcriptome analysis, spatial and temporal expression patterns, and bioinformatics. Microarrays revealed similar miRNA profiles in newborn-mouse whole cochleae and vestibules, but different temporal and spatial expression patterns of six miRNAs (miR-15a, miR-18a, miR-30b, miR-99a, miR-182, and miR-199a) may reflect their roles. Two of these miRNAs, miR-15a-1 and miR-18a, were also shown to be crucial for zebrafish inner ear development and morphogenesis. To suggest putative target mRNAs whose translation may be inhibited by selected miRNAs, we combined bioinformatics-based predictions and mRNA expression data. Finally, we present indirect evidence that Slc12a2, Cldn12, and Bdnf mRNAs may be targets for miR-15a. Our data support the hypothesis that inner ear tissue differentiation and maintenance are regulated and controlled by conserved sets of cell-specific miRNAs in both mouse and zebrafish.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cochlea / embryology*
  • Cochlea / physiology
  • Computational Biology / methods
  • Gene Expression Profiling
  • Hair Cells, Auditory, Inner / physiology*
  • Homozygote
  • Mice
  • Mice, Knockout
  • MicroRNAs / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Point Mutation
  • Vertebrates
  • Vestibule, Labyrinth / embryology*
  • Vestibule, Labyrinth / physiology
  • Zebrafish

Substances

  • MicroRNAs

Associated data

  • GEO/GSE15496