Members of the microRNA (miRNA) 183 family (miR-183, miR-96, and miR-182) are expressed abundantly in specific sensory cell types in the eye, nose, and inner ear. In the inner ear, expression is robust in the mechanosensory hair cells and weak in the associated statoacoustic ganglion (SAG) neurons; both cell types can share a common lineage during development. Recently, dominant-progressive hearing loss in humans and mice was linked to mutations in the seed region of miR-96, with associated defects in both development and maintenance of hair cells in the mutant mice. To understand how the entire triplet functions in the development of mechanosensory hair cells and neurons of the inner ear, we manipulated the levels of these miRNAs in zebrafish embryos using synthesized miRNAs and antisense morpholino oligonucleotides (MOs). Overexpression of miR-96 or miR-182 induces duplicated otocysts, ectopic or expanded sensory patches, and extra hair cells, whereas morphogenesis of the SAG is adversely affected to different degrees. In contrast, knockdown of miR-183, miR-96, and miR-182 causes reduced numbers of hair cells in the inner ear, smaller SAGs, defects in semicircular canals, and abnormal neuromasts on the posterior lateral line. However, the prosensory region of the posterior macula, where the number of hair cells is reduced by ϳ50%, is not significantly impaired. Our findings suggest both distinct and common roles for the three miRNAs in cell-fate determination in the inner ear, and these principles might apply to development of other sensory organs.
A novel electrocatalyzed method for the preparation of dibenzosiloles was developed through intramolecular C−H/Si−H dehydrogenative coupling strategy starting from biarylhydrosilanes. Both electro‐donating and electro‐withdrawing substitution groups were tolerated for this transformation, and the desired dibenzosilole products could be obtained in moderate to excellent yields. A sila‐Friedel‐Crafts reaction mechanism was proposed on the basis of previous literature and our controlled experiments.
Purpose of review-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.Recent findings-miRNAs are ~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, are 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, while 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.Summary-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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