PUBLICATION

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

Authors
Friedman, L.M., Dror, A.A., Mor, E., Tenne, T., Toren, G., Satoh, T., Biesemeier, D.J., Shomron, N., Fekete, D.M., Hornstein, E., and Avraham, K.B.
ID
ZDB-PUB-090511-8
Date
2009
Source
Proceedings of the National Academy of Sciences of the United States of America   106(19): 7915-7920 (Journal)
Registered Authors
Fekete, Donna Marie
Keywords
cochlea, deafness, Dicer, mouse, zebrafish
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
PubMed
19416898 Full text @ Proc. Natl. Acad. Sci. USA
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes