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MicroRNAs are essential for development and function of inner ear hair cells in vertebrates
Lilach M Friedman1, Amiel A Dror, Eyal Mor
1Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
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.
Insights
MicroRNAs (miRNAs) are vital for inner ear hair cell survival and development. This study identifies key miRNAs regulating inner ear tissue differentiation and maintenance in mice and zebrafish.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- MicroRNAs (miRNAs) regulate gene expression by inhibiting mRNA translation, impacting a significant portion of protein-coding genes.
- The inner ear, comprising the cochlea and vestibule, relies on precise gene regulation for development and function.
Purpose of the Study:
- To identify and characterize microRNAs (miRNAs) involved in the development and maintenance of the mouse and zebrafish inner ear.
- To investigate the role of specific miRNAs in the survival and differentiation of inner ear hair cells.
Main Methods:
- Conditional knock-out mouse models (Dicer1) to assess miRNA function.
- Microarray analysis to compare miRNA expression profiles in cochlea and vestibule.
- Bioinformatic predictions combined with mRNA expression data to identify miRNA targets.
Main Results:
- MicroRNAs are essential for the postnatal survival of functional inner ear hair cells.
- Six specific miRNAs (miR-15a, miR-18a, miR-30b, miR-99a, miR-182, and miR-199a) showed distinct temporal and spatial expression patterns in the developing mouse inner ear.
- miR-15a and miR-18a were found to be crucial for zebrafish inner ear development and morphogenesis.
- Indirect evidence suggests Slc12a2, Cldn12, and Bdnf mRNAs are potential targets of miR-15a.
Conclusions:
- Conserved sets of cell-specific miRNAs regulate inner ear tissue differentiation and maintenance in both mouse and zebrafish.
- Specific miRNAs play critical roles in vertebrate inner ear development, highlighting their importance in sensory organ formation.
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