MicroRNAs are essential for development and function of inner ear hair cells in vertebrates
- 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.
- Proceedings of the National Academy of Sciences of the United States of America 106(19): 7915-7920 (Journal)
- Registered Authors
- Fekete, Donna Marie
- cochlea, deafness, Dicer, mouse, zebrafish
- MeSH Terms
- Computational Biology/methods
- Gene Expression Profiling
- Hair Cells, Auditory, Inner/physiology*
- Mice, Knockout
- Oligonucleotide Array Sequence Analysis
- Point Mutation
- Vestibule, Labyrinth/embryology*
- Vestibule, Labyrinth/physiology
- 19416898 Full text @ Proc. Natl. Acad. Sci. USA
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. (2009) MicroRNAs are essential for development and function of inner ear hair cells in vertebrates. Proceedings of the National Academy of Sciences of the United States of America. 106(19):7915-7920.
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
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes