Abstract
The identification of transcriptional activators and repressors of hair cell fates has recently been augmented by the discovery of microRNAs (miRNAs) that can function as post-transcriptional repressors in sensory hair cells. miRNAs are approximately 21-nucleotide single-stranded ribonucleic acids that can each repress protein synthesis of many target genes by interacting with messenger RNA transcripts. A triplet of these miRNAs, the miR-183 family, is highly expressed in vertebrate hair cells, as well as a variety of other peripheral neurosensory cells. Point mutations in one member of this family, miR-96, underlie DFNA50 autosomal deafness in humans and lead to abnormal hair cell development and survival in mice. In zebrafish, overexpression of the miR-183 family induces extra and ectopic hair cells, whereas knockdown reduces hair cell numbers. Genetically engineered mice with a block in miRNA biosynthesis during early ear development, or during hair cell differentiation, reveal the necessity of miRNAs at these crucial time points. Because miRNAs can simultaneously down-regulate dozens to perhaps hundreds of transcripts, they will soon be explored as potential therapeutic agents to repair or regenerate hair cells in animal models.
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