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Nat Commun. 2015 Oct 15;6:8549. doi: 10.1038/ncomms9549.

RFX transcription factors are essential for hearing in mice.

Author information

1
Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
2
Department of Otorhinolaryngology, School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA.
3
Department of Special Education and Communication Disorders, University of Nebraska Lincoln, Lincoln, Nebraska 68583-0738, USA.
4
Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, School of Medicine, University of Maryland Baltimore, Baltimore, Maryland 21201, USA.
5
Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky 40536-0298, USA.
6
Centre de Génétique et de Physiologie Moléculaire et Cellulaire, CNRS UMR 5534, Université Claude Bernard Lyon-1, 69622 Villeurbanne, France.
7
Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland.
8
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, 4051 Basel, Switzerland.
9
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
10
Department of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
11
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.

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.

PMID:
26469318
PMCID:
PMC4634137
DOI:
10.1038/ncomms9549
[Indexed for MEDLINE]
Free PMC Article

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