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RFX transcription factors are essential for hearing in mice.

Nature communications (2015-10-16)
Ran Elkon, Beatrice Milon, Laura Morrison, Manan Shah, Sarath Vijayakumar, Manoj Racherla, Carmen C Leitch, Lorna Silipino, Shadan Hadi, Michèle Weiss-Gayet, Emmanuèle Barras, Christoph D Schmid, Aouatef Ait-Lounis, Ashley Barnes, Yang Song, David J Eisenman, Efrat Eliyahu, Gregory I Frolenkov, Scott E Strome, Bénédicte Durand, Norann A Zaghloul, Sherri M Jones, Walter Reith, Ronna Hertzano
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.

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