Expression of Math1and HES5in the Cochleae of Wildtype and Jag2 Mutant Mice

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 Math1as well as the HESfamily of inhibitory bHLH proteins. To determine the potential roles of these genes in cochlear development, in situ hybridization for Math1and HES5was performed on the cochleae of wildtype vs. Jagged2mutants (Jag2ΔDSL). Results in wild-type cochleae show that expression of Math1transcripts in the duct begins on E13 and ultimately becomes restricted to hair cells in the sensory epithelium. In contrast, expression of HES5begins on E15 and becomes restricted to supporting cells in the epithelium. Results in Jag2mutant cochleae suggest that Math1transcripts are ultimately maintained in a larger number of cells as compared with wildtype, while transcripts for HES5are dramatically reduced throughout the epithelium. These results are consistent with the hypothesis that activation of Notch via Jagged2 acts to inhibit expression of Math1in cochlear progenitor cells, possibly through the activity of HES5.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 Math1as well as the HESfamily of inhibitory bHLH proteins. To determine the potential roles of these genes in cochlear development, in situ hybridization for Math1and HES5was performed on the cochleae of wildtype vs. Jagged2mutants (Jag2ΔDSL). Results in wild-type cochleae show that expression of Math1transcripts in the duct begins on E13 and ultimately becomes restricted to hair cells in the sensory epithelium. In contrast, expression of HES5begins on E15 and becomes restricted to supporting cells in the epithelium. Results in Jag2mutant cochleae suggest that Math1transcripts are ultimately maintained in a larger number of cells as compared with wildtype, while transcripts for HES5are dramatically reduced throughout the epithelium. These results are consistent with the hypothesis that activation of Notch via Jagged2 acts to inhibit expression of Math1in cochlear progenitor cells, possibly through the activity of HES5.