RFX transcription factors are essential for hearing in mice

• Published in: Nature communications Vol. 6; no. 1; p. 8549
• Main Authors: Elkon, Ran, Milon, Beatrice, Morrison, Laura, Shah, Manan, Vijayakumar, Sarath, Racherla, Manoj, Leitch, Carmen C., Silipino, Lorna, Hadi, Shadan, Weiss-Gayet, Michèle, Barras, Emmanuèle, Schmid, Christoph D., Ait-Lounis, Aouatef, Barnes, Ashley, Song, Yang, Eisenman, David J., Eliyahu, Efrat, Frolenkov, Gregory I., Strome, Scott E., Durand, Bénédicte, Zaghloul, Norann A., Jones, Sherri M., Reith, Walter, Hertzano, Ronna
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.10.2015; Nature Publishing Group
• Subjects: 13/31; 13/51; 14/19; 14/28; 38/39; 38/90; 49/91; 631/136; 631/378/2619/1533; 631/45/612/822; 64/110; 64/116; 64/60; Animals; Animals, Newborn; Biological Evolution; Chromatin Immunoprecipitation; DNA-Binding Proteins - metabolism; Female; Gene Expression Regulation; Hair Cells, Auditory - metabolism; Hair Cells, Auditory - ultrastructure; Hearing - physiology; Humanities and Social Sciences; Male; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; multidisciplinary; Multigene Family; Regulatory Factor X Transcription Factors; Regulatory Factor X1; Science; Science (multidisciplinary); Sequence Analysis, DNA; Transcription Factors - metabolism; Transcriptome; Zebrafish
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms9549

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. Inner ear hair cells are non-regenerative mechanosensory cells essential for hearing. Here, with cell-type-specific expression analyses, the authors identify RFX transcription factors as central mediators of their survival during terminal differentiation and thus essential for hearing in mice.