Connexin26 gap junction mediates miRNA intercellular genetic communication in the cochlea and is required for inner ear development.

Organ development requires well-established intercellular communication to coordinate cell proliferations and differentiations. MicroRNAs (miRNAs) are small, non-coding RNAs that can broadly regulate gene expression and play a critical role in the organ development. In this study, we found that miRNAs could pass through gap junctions between native cochlear supporting cells to play a role in the cochlear development. Connexin26 (Cx26) and Cx30 are predominant isoforms and co-express in the cochlea. Cx26 deficiency but not Cx30 deficiency can cause cochlear developmental disorders. We found that associated with Cx26 deletion induced the cochlear developmental disorders, deletion of Cx26 but not Cx30 disrupted miRNA intercellular transfer in the cochlea, although inner ear gap junctions still retained permeability after deletion of Cx26. Moreover, we found that deletion of Cx26 but not Cx30 reduced miR-96 expression in the cochlea during postnatal development. The reduction is associated with the cochlear tunnel developmental disorder in Cx26 knockout (KO) mice. These data reveal that Cx26-mediated intercellular communication is required for cochlear development and that deficiency of Cx26 can impair miRNA-mediated intercellular genetic communication in the cochlea, which may lead to cochlear developmental disorders and eventually congenital deafness as previously reported.