Among these are the transcription factors (TFs) ATOH1 (ref. To date, several master regulators of HC fate and differentiation have been characterized.
For this reason, understanding the molecular signalling cascades that lead to HC differentiation is important for hearing restoration. Mammalian auditory HCs do not regenerate and their loss is a final common pathway in most forms of hearing dysfunction 4. The sensations of sound and movement are dependent on highly specialized post-mitotic mechanosensory cells called hair cells (HCs) 3. Sensorineural hearing loss affects 1:500 newborns 1 and the majority of the elderly population 2. These data identify an essential role for RFX in hearing and survival of the terminally differentiating outer HCs. We show that these mice are deaf secondary to rapid loss of initially well-formed outer HCs. To understand the role of RFX in hearing, we generate Rfx1/3 conditional knockout mice. We identify RFX transcription factors as essential and evolutionarily conserved regulators of the HC-specific transcriptomes, and detect Rfx1,2,3,5 and 7 in the developing HCs. Here we apply a cell type-specific functional genomic analysis to the transcriptomes of auditory and vestibular sensory epithelia from early postnatal mice.
Importantly, although the transcriptional regulators of embryonic HC development have been described, little is known about the postnatal regulators of maturating HCs. Sensorineural hearing loss is a common and currently irreversible disorder, because mammalian hair cells (HCs) do not regenerate and current stem cell and gene delivery protocols result only in immature HC-like cells.
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