RFX transcription factors are essential for hearing in mice

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 and Ronna Hertzano ()
Additional contact information
Ran Elkon: Sackler School of Medicine, Tel Aviv University
Beatrice Milon: School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA
Laura Morrison: School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA
Manan Shah: School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA
Sarath Vijayakumar: University of Nebraska Lincoln
Manoj Racherla: School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA
Carmen C. Leitch: Diabetes and Nutrition, School of Medicine, University of Maryland Baltimore
Lorna Silipino: School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA
Shadan Hadi: College of Medicine, University of Kentucky
Michèle Weiss-Gayet: Centre de Génétique et de Physiologie Moléculaire et Cellulaire
Emmanuèle Barras: University of Geneva Medical School
Christoph D. Schmid: Swiss Tropical and Public Health Institute, and University of Basel
Aouatef Ait-Lounis: University of Geneva Medical School
Ashley Barnes: School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA
Yang Song: Institute for Genome Sciences, University of Maryland School of Medicine
David J. Eisenman: School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA
Efrat Eliyahu: Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai
Gregory I. Frolenkov: College of Medicine, University of Kentucky
Scott E. Strome: School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA
Bénédicte Durand: Centre de Génétique et de Physiologie Moléculaire et Cellulaire
Norann A. Zaghloul: Diabetes and Nutrition, School of Medicine, University of Maryland Baltimore
Sherri M. Jones: University of Nebraska Lincoln
Walter Reith: University of Geneva Medical School
Ronna Hertzano: School of Medicine, University of Maryland Baltimore, 16 South Eutaw Street Suite 500, Baltimore, Maryland 21201, USA

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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.

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9549

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DOI: 10.1038/ncomms9549

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