Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer

摘要: Sensory hair cells in the mammalian cochlea convert mechanical stimuli into electrical impulses that subserve audition. Loss of and their innervating neurons is most frequent cause hearing impairment. Atonal homologue 1 (encoded by Atoh1, also known as Math1) a basic helix-loop-helix transcription factor required for hair-cell development, its misexpression vitro vivo generates hair-cell-like cells. Atoh1-based gene therapy to ameliorate auditory vestibular dysfunction has been proposed. However, biophysical properties putative induced Atoh1 have not characterized. Here we show utero transfer produces functional supernumerary mouse cochlea. The display stereociliary bundles, attract neuronal processes express ribbon synapse marker carboxy-terminal binding protein 2 (refs 12,13). Moreover, are capable mechanoelectrical transduction basolateral conductances with age-appropriate specializations. Our results demonstrate manipulation cell fate sensory postnatal We expect our paradigm will enable design validation therapies loss models human deafness.