| Literature DB >> 26469318 |
Ran Elkon1, Beatrice Milon2, Laura Morrison2, Manan Shah2, Sarath Vijayakumar3, Manoj Racherla2, Carmen C Leitch4, Lorna Silipino2, Shadan Hadi5, Michèle Weiss-Gayet6, Emmanuèle Barras7, Christoph D Schmid8, Aouatef Ait-Lounis7, Ashley Barnes2, Yang Song9, David J Eisenman2, Efrat Eliyahu10, Gregory I Frolenkov5, Scott E Strome2, Bénédicte Durand6, Norann A Zaghloul4, Sherri M Jones3, Walter Reith7, Ronna Hertzano2,9,11.
Abstract
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. Importantly, although the transcriptional regulators of embryonic HC development have been described, little is known about the postnatal regulators of maturating HCs. Here we apply a cell type-specific functional genomic analysis to the transcriptomes of auditory and vestibular sensory epithelia from early postnatal 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. To understand the role of RFX in hearing, we generate Rfx1/3 conditional knockout mice. We show that these mice are deaf secondary to rapid loss of initially well-formed outer HCs. These data identify an essential role for RFX in hearing and survival of the terminally differentiating outer HCs.Entities:
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Year: 2015 PMID： 26469318 PMCID： PMC4634137 DOI： 10.1038/ncomms9549
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 17.694