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RFX transcription factors are essential for hearing in mice

Author

Listed:
  • 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
    Present address: Laboratory of Cellular and Molecular Biology, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene, Algiers, Algeria.)

  • 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
    Institute for Genome Sciences, University of Maryland School of Medicine
    University of Maryland School of Medicine)

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.

Suggested Citation

  • 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., 2015. "RFX transcription factors are essential for hearing in mice," Nature Communications, Nature, vol. 6(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9549
    DOI: 10.1038/ncomms9549
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