RFX transcription factors are essential for hearing in mice

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 h...

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Published inNature 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
LanguageEnglish
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
Online AccessGet full text

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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. 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.
AbstractList 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.
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.
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.
ArticleNumber 8549
Author Weiss-Gayet, Michèle
Leitch, Carmen C.
Schmid, Christoph D.
Elkon, Ran
Milon, Beatrice
Barras, Emmanuèle
Durand, Bénédicte
Silipino, Lorna
Hertzano, Ronna
Jones, Sherri M.
Shah, Manan
Ait-Lounis, Aouatef
Song, Yang
Eisenman, David J.
Eliyahu, Efrat
Frolenkov, Gregory I.
Morrison, Laura
Vijayakumar, Sarath
Barnes, Ashley
Hadi, Shadan
Racherla, Manoj
Strome, Scott E.
Reith, Walter
Zaghloul, Norann A.
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  organization: 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, Department of Anatomy and Neurobiology, University of Maryland School of Medicine
BackLink https://www.ncbi.nlm.nih.gov/pubmed/26469318$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright The Author(s) 2015
Copyright Nature Publishing Group Oct 2015
Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2015 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
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content type line 23
These authors contributed equally to this work.
Present address: Laboratory of Cellular and Molecular Biology, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene, Algiers, Algeria.
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Snippet Sensorineural hearing loss is a common and currently irreversible disorder, because mammalian hair cells (HCs) do not regenerate and current stem cell and gene...
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SubjectTerms 13/31
13/51
14/19
14/28
38/39
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49/91
631/136
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631/45/612/822
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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
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Title RFX transcription factors are essential for hearing in mice
URI https://link.springer.com/article/10.1038/ncomms9549
https://www.ncbi.nlm.nih.gov/pubmed/26469318
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https://pubmed.ncbi.nlm.nih.gov/PMC4634137
Volume 6
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