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
-
- Homozygote
- Vertebrates
- MicroRNAs/metabolism*
- Computational Biology/methods
- Oligonucleotide Array Sequence Analysis
- 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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping