Hes1 and Hes5 activities are required for the normal development of the hair cells in the mammalian inner ear.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_19784
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Hes1 and Hes5 activities are required for the normal development of the hair cells in the mammalian inner ear.
Périodique
Journal of Neuroscience
Auteur(s)
Zine A., Aubert A., Qiu J., Therianos S., Guillemot F., Kageyama R., de Ribaupierre F.
ISSN
1529-2401[electronic]
Statut éditorial
Publié
Date de publication
2001
Volume
21
Numéro
13
Pages
4712-4720
Langue
anglais
Résumé
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.
Mots-clé
Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Count, Cell Differentiation/genetics, Cochlea/cytology, Cochlea/embryology, Crosses, Genetic, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Ear, Inner/cytology, Ear, Inner/embryology, Hair Cells, Auditory/metabolism, Heterozygote, Homeodomain Proteins/genetics, Homeodomain Proteins/metabolism, Homozygote, Immunohistochemistry, In Situ Hybridization, Mice, Mice, Mutant Strains, Nerve Tissue Proteins/metabolism, RNA, Messenger/metabolism, Repressor Proteins/genetics, Repressor Proteins/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors/genetics, Transcription Factors/metabolism, Up-Regulation
Pubmed
Web of science
Création de la notice
19/11/2007 12:14
Dernière modification de la notice
20/08/2019 12:50
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