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J Assoc Res Otolaryngol. Jun 2000; 1(2): 161–171.
Published online Aug 15, 2000. doi:  10.1007/s101620010023
PMCID: PMC2504537
Expression of Math1 and HES5 in the Cochleae of Wildtype and Jag2 Mutant Mice
Pamela J. Lanford,corresponding author1 Ranu Shailam,1 Christine R. Norton,2 Thomas Ridley,2 and Matthew W. Kelley1
1Department of Cell Biology, Georgetown University School of Medicine, Washington DC, 20007 USA
2The Jackson Laboratory, Bar Harbor, ME 04609 USA
Pamela J. Lanford, lanfordp/at/nidcd.nih.gov.
corresponding authorCorresponding author.
Received May 12, 2000; Accepted May 25, 2000.
Abstract
The sensory epithelium within the mammalian cochlea (the organ of Corti) is a strictly ordered cellular array consisting of sensory hair cells and nonsensory supporting cells. Previous research has demonstrated that Notch-mediated lateral inhibition plays a key role in the determination of cell types within this array. Specifically, genetic deletion of the Notch ligand, Jagged2, results in a significant increase in the number of hair cells that develop within the sensory epithelium, presumably as a result of a decrease in Notch activation. In contrast, the downstream mediators and targets of the Notch pathway in the inner ear have not been determined but they may include genes encoding the proneural gene Math1 as well as the HES family of inhibitory bHLH proteins. To determine the potential roles of these genes in cochlear development, in situ hybridization for Math1 and HES5 was performed on the cochleae of wildtype vs. Jagged2 mutants (Jag2ΔDSL ). Results in wild-type cochleae show that expression of Math1 transcripts in the duct begins on E13 and ultimately becomes restricted to hair cells in the sensory epithelium. In contrast, expression of HES5 begins on E15 and becomes restricted to supporting cells in the epithelium. Results in Jag2 mutant cochleae suggest that Math1 transcripts are ultimately maintained in a larger number of cells as compared with wildtype, while transcripts for HES5 are dramatically reduced throughout the epithelium. These results are consistent with the hypothesis that activation of Notch via Jagged2 acts to inhibit expression of Math1 in cochlear progenitor cells, possibly through the activity of HES5.
Keywords: Notch, Jagged2, lateral inhibition, inner ear, hair cell
Articles from JARO: Journal of the Association for Research in Otolaryngology are provided here courtesy of
Association for Research in Otolaryngology