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The Notch ligand Jagged1 is required for inner ear sensory development.
Kiernan, A. E.; Ahituv, N.; Fuchs, H. et al.
2001In Proceedings of the National Academy of Sciences of the United States of America, 98 (7), p. 3873-8
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Keywords :
Amino Acid Sequence; Animals; Calcium-Binding Proteins; Chromosome Mapping; Chromosomes; Ear, Inner/abnormalities/growth & development; Homozygote; Humans; Intercellular Signaling Peptides and Proteins; Membrane Proteins/metabolism; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Molecular Sequence Data; Mutation, Missense; Phenotype; Proteins/physiology; Rats; Receptors, Notch; Sequence Analysis, DNA
Abstract :
[en] Within the mammalian inner ear there are six separate sensory regions that subserve the functions of hearing and balance, although how these sensory regions become specified remains unknown. Each sensory region is populated by two cell types, the mechanosensory hair cell and the supporting cell, which are arranged in a mosaic in which each hair cell is surrounded by supporting cells. The proposed mechanism for creating the sensory mosaic is lateral inhibition mediated by the Notch signaling pathway. However, one of the Notch ligands, Jagged1 (Jag1), does not show an expression pattern wholly consistent with a role in lateral inhibition, as it marks the sensory patches from very early in their development--presumably long before cells make their final fate decisions. It has been proposed that Jag1 has a role in specifying sensory versus nonsensory epithelium within the ear [Adam, J., Myat, A., Roux, I. L., Eddison, M., Henrique, D., Ish-Horowicz, D. & Lewis, J. (1998) Development (Cambridge, U.K.) 125, 4645--4654]. Here we provide experimental evidence that Notch signaling may be involved in specifying sensory regions by showing that a dominant mouse mutant headturner (Htu) contains a missense mutation in the Jag1 gene and displays missing posterior and sometimes anterior ampullae, structures that house the sensory cristae. Htu/+ mutants also demonstrate a significant reduction in the numbers of outer hair cells in the organ of Corti. Because lateral inhibition mediated by Notch predicts that disruptions in this pathway would lead to an increase in hair cells, we believe these data indicate an earlier role for Notch within the inner ear.
Disciplines :
Genetics & genetic processes
Author, co-author :
Kiernan, A. E.
Ahituv, N.
Fuchs, H.
Balling, Rudi 
Avraham, K. B.
Steel, K. P.
Hrabe de Angelis, M.
Language :
English
Title :
The Notch ligand Jagged1 is required for inner ear sensory development.
Publication date :
2001
Journal title :
Proceedings of the National Academy of Sciences of the United States of America
ISSN :
1091-6490
Publisher :
National Academy of Sciences, Washington, United States - District of Columbia
Volume :
98
Issue :
7
Pages :
3873-8
Peer reviewed :
Peer Reviewed verified by ORBi
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