Lhx3, a LIM domain transcription factor, is regulated by Pou4f3 in the auditory but not in the vestibular system

Authors

  • Ronna Hertzano,

    1. Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    2. Section on Developmental Neuroscience, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA
    3. Section on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA
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    • *

      Present address: Department of Otorhinolaryngology, University of Maryland, Baltimore, MD, USA.

  • Amiel A. Dror,

    1. Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
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  • Mireille Montcouquiol,

    1. Section on Developmental Neuroscience, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA
    2. Laboratory of Development Neurosciences - Avenir Team, Centre de Recherche INSERM Francois Magendie, Universite Bordeaux II, 33077 Bordeaux Cedex, France
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  • Zubair M. Ahmed,

    1. Section on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA
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  • Buffy Ellsworth,

    1. Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
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  • Sally Camper,

    1. Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
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  • Thomas B. Friedman,

    1. Section on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA
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  • Matthew W. Kelley,

    1. Section on Developmental Neuroscience, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA
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  • Karen B. Avraham

    1. Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
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Professor K. B. Avraham, as above.
E-mail: karena@post.tau.ac.il

Abstract

A dominant mutation of the gene encoding the POU4F3 transcription factor underlies human non-syndromic progressive hearing loss DFNA15. Using oligonucleotide microarrays to generate expression profiles of inner ears of Pou4f3ddl/ddl mutant and wild-type mice, we have identified and validated Lhx3, a LIM domain transcription factor, as an in vivo target gene regulated by Pou4f3. Lhx3 is a hair cell-specific gene expressed in all hair cells of the auditory and vestibular system as early as embryonic day 16. The level of Lhx3 mRNA is greatly reduced in the inner ears of embryonic Pou4f3 mutant mice. Our data also show that the expression of Lhx3 is regulated differently in auditory and vestibular hair cells. This is the first example of a hair cell-specific gene expressed both in auditory and in vestibular hair cells, with differential regulation of expression in these two closely related systems.

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