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The Journal of Neuroscience, July 1, 2001, 21(13):4712-4720
Hes1 and Hes5 Activities Are
Required for the Normal Development of the Hair Cells in the Mammalian
Inner Ear
Azel
Zine1,
Alexandre
Aubert1,
Jiping
Qiu1,
Stavros
Therianos1,
Francois
Guillemot2,
Ryoichiro
Kageyama3, and
Francois
de
Ribaupierre1
1 Institute of Physiology, University of Lausanne, 1005 Lausanne, Switzerland, 2 Institut de Genetique et de
Biologie Moleculaire et Cellulaire, 67404 Illkirch, Centre de
l'Université de Strasbourg, France, and
3 Institute for Virus Research, Kyoto University,
Kyoto 606-8507, Japan
The mammalian inner ear contains two sensory organs, the cochlea
and vestibule. Their sensory neuroepithelia are characterized by a
mosaic of hair cells and supporting cells. Cochlear hair cells
differentiate in four rows: a single row of inner hair cells (IHCs) and
three rows of outer hair cells (OHCs). Recent studies have shown that
Math1, a mammalian homolog of Drosophila atonal is a
positive regulator of hair cell differentiation. The basic helix-loop-helix (bHLH) genes Hes1 and
Hes5 (mammalian hairy and Enhancer-of-split homologs) can influence cell fate
determination by acting as negative regulators to inhibit the action of
bHLH-positive regulators. We show by using reverse transcription-PCR
analysis that Hes1, Hes5, and
Math1 are expressed in the developing mouse cochleae.
In situ hybridization revealed a widespread expression of Hes1 in the greater epithelial ridge (GER) and in
lesser epithelial ridge (LER) regions. Hes5 is
predominantly expressed in the LER, in supporting cells, and in a
narrow band of cells within the GER.
Examination of cochleae from
Hes1 / mice showed a significant
increase in the number of IHCs, whereas cochleae from
Hes5/ mice showed a significant
increase in the number of OHCs. In the vestibular system, targeted
deletion of Hes1 and to a lesser extent
Hes5 lead to formation of supernumerary hair cells in
the saccule and utricle.
The supernumerary hair cells in the mutant mice showed an upregulation
of Math1. These data indicate that Hes1 and
Hes5 participate together for the control of inner ear
hair cell production, likely through the negative regulation of Math1.
Key words:
Hes1; Hes5; Math1; basic
helix-loop-helix (bHLH) transcriptions factors; mouse mutant; cochlea; utricle; saccule; hair cell differentiation
Copyright © 2001 Society for Neuroscience 0270-6474/01/21134712-09$05.00/0
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