The MIR-183/ItgA3 axis is a key regulator of prosensory area during early inner ear development

Abstract

MicroRNAs are important regulators of gene expression and are involved in cellular processes such as proliferation or differentiation, particularly during development of numerous organs including the inner ear. However, it remains unknown if miRNAs are required during the earliest stages of otocyst and cochlear duct development. Here, we report that a conditional loss of Dicer expression in the otocyst impairs the early development of the inner ear as a result of the accumulation of DNA damage that trigger p53-mediated apoptosis. Moreover, cochlear progenitors in the prosensory domain do not exit the cell cycle. Our unbiased approach identified ItgA3 as a target of miR-183, which are both enriched in the otic vesicle. We observed that the repression of integrin alpha 3 by miR-183 controls cell proliferation in the developing cochlea. Collectively, our results reveal that Dicer and miRNAs play essential roles in the regulation of early inner ear development.