title: RFX transcription factors are essential for hearing in mice.
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.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ran
authors.initials: R
authors.lastname: Elkon
authors.affiliation: Department of Otorhinolaryngology, School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Milon
authors.affiliation: Department of Otorhinolaryngology, School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Morrison
authors.affiliation: Department of Otorhinolaryngology, School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA.
authors.forename: Manan
authors.initials: M
authors.lastname: Shah
authors.affiliation: Department of Special Education and Communication Disorders, University of Nebraska Lincoln, Lincoln, Nebraska 68583-0738, USA.
authors.forename: Sarath
authors.initials: S
authors.lastname: Vijayakumar
authors.affiliation: Department of Otorhinolaryngology, School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA.
authors.forename: Manoj
authors.initials: M
authors.lastname: Racherla
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, School of Medicine, University of Maryland Baltimore, Baltimore, Maryland 21201, USA.
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Leitch
authors.affiliation: Department of Otorhinolaryngology, School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA.
authors.forename: Lorna
authors.initials: L
authors.lastname: Silipino
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky 40536-0298, USA.
authors.forename: Shadan
authors.initials: S
authors.lastname: Hadi
authors.affiliation: Centre de Génétique et de Physiologie Moléculaire et Cellulaire, CNRS UMR 5534, Université Claude Bernard Lyon-1, 69622 Villeurbanne, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Weiss-Gayet
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland.
authors.forename: Emmanuèle
authors.initials: E
authors.lastname: Barras
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, 4051 Basel, Switzerland.
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Schmid
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland.
authors.forename: Aouatef
authors.initials: A
authors.lastname: Ait-Lounis
authors.affiliation: Department of Otorhinolaryngology, School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Barnes
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Otorhinolaryngology, School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Eisenman
authors.affiliation: 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.
authors.forename: Efrat
authors.initials: E
authors.lastname: Eliyahu
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky 40536-0298, USA.
authors.forename: Gregory I
authors.initials: GI
authors.lastname: Frolenkov
authors.affiliation: Department of Otorhinolaryngology, School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Strome
authors.affiliation: Centre de Génétique et de Physiologie Moléculaire et Cellulaire, CNRS UMR 5534, Université Claude Bernard Lyon-1, 69622 Villeurbanne, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Durand
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, School of Medicine, University of Maryland Baltimore, Baltimore, Maryland 21201, USA.
authors.forename: Norann A
authors.initials: NA
authors.lastname: Zaghloul
authors.affiliation: Department of Special Education and Communication Disorders, University of Nebraska Lincoln, Lincoln, Nebraska 68583-0738, USA.
authors.forename: Sherri M
authors.initials: SM
authors.lastname: Jones
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Reith
authors.affiliation: Department of Otorhinolaryngology, School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA.|Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.|Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Ronna
authors.initials: R
authors.lastname: Hertzano
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005075:Biological Evolution; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000648:ultrastructure; D006309:Hearing / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D005810:Multigene Family; D000071701:Regulatory Factor X Transcription Factors; D000071716:Regulatory Factor X1; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism*; D059467:Transcriptome; D015027:Zebrafish
chemical_list: D004268:DNA-Binding Proteins; C000605537:RFX1 protein, human; D000071701:Regulatory Factor X Transcription Factors; D000071716:Regulatory Factor X1; C000605538:Rfx1 protein, mouse; D014157:Transcription Factors