RFX Transcription Factors are Essential for Hearing in Mice

Authors

Ran Elkon, Tel Aviv University
Beatrice Milon, University of Maryland - Baltimore
Laura Morrison, University of Maryland - Baltimore
Manan Shah, University of Maryland - Baltimore
Sarath Vijayakumar, University of Nebraska - LincolnFollow
Manoj Racherla, University of Maryland - Baltimore
Carmen C. Leitch, University of Maryland - Baltimore
Lorna Silipino, University of Maryland - Baltimore
Shadan Hadi, University of Kentucky
Michèle Weiss-Gayte, Université Claude Bernard Lyon
Emmanuèle Barras, University of Geneva Medical School
Christoph D. Schmid, University of Basel
Aouatef Ait-Lounis, University of Sciences and Technology Houari Boumediene
Ashley Barnes, University of Maryland - Baltimore
Yang Song, University of Maryland School of Medicine
David J. Eisenman, University of Maryland - Baltimore
Efrat Eliyahu, Icahn School of Medicine at Mount Sinai
Gregory I. Frolenkov, University of Kentucky
Scott E. Strome, University of Maryland - Baltimore
Bénédicte Durand, Université Claude Bernard Lyon
Norann A. Zaghloul, University of Maryland - Baltimore
Sherri M. Jones, University of Nebraska - LincolnFollow
Walter Reith, University of Geneva Medical School
Ronna Hertzano, University of Maryland School of MedicineFollow

Document Type

Article

Date of this Version

10-15-2015

Citation

Nature Communications (October 15, 2015) 6: 8549. | DOI: 10.1038/ncomms9549.

Comments

Copyright 2015, the authors. Open access, Creative Commons Attribution 4.0 International license.

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.