| http://purl.uniprot.org/citations/21300049 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21300049 | http://www.w3.org/2000/01/rdf-schema#comment | "Notch-mediated lateral inhibition has been reported to regulate auditory hair cell and supporting cell development from common precursors. While the Notch effector genes Hes1, Hes5 and Hey1 are expressed in the developing cochlea, inactivation of either of them causes only mild abnormality, suggesting their functional redundancy. To explore the roles of Hes/Hey genes in cochlear development, we examined compound heterozygous or homozygous mutant mice that lacked Hes1, Hes5 and Hey1 alleles. We found that a reduction in Hes/Hey gene dosage led to graded increase of hair cell formation. However, if at least one allele of Hes1, Hes5 or Hey1 was intact, excessive hair cells were accompanied by overproduction of supporting cells, suggesting that the hair cell increase does not occur at the expense of supporting cells, and that each Hes/Hey gene functions to induce supporting cells. By contrast, when all alleles of Hes1, Hes5 and Hey1 were inactivated, the number of hair cells increased more drastically, whereas that of supporting cells was unchanged compared with control, suggesting that supporting cell formation was balanced by their overproduction and fate conversion into hair cells. The increase of the cell numbers seemed to occur after the prosensory domain formation in the mutants because the proliferation state and the size of the prosensory domain were not affected. Thus, Hes1, Hes5 and Hey1 cooperatively inhibit hair cell formation, and one allele of Hes1, Hes5 or Hey1 is sufficient for supporting cell production probably by lateral inhibition in the sensory epithelium. Strikingly, Hes/Hey mutations lead to disorganized cell alignment and polarity and to hearing loss despite hair cell overproduction. These results suggest that Hes/Hey gene dosage is essential not only for generation of appropriate numbers of hair cells and supporting cells by controlling cell proliferation and lateral inhibition but also for the hearing ability by regulating the cell alignment and polarity."xsd:string |
| http://purl.uniprot.org/citations/21300049 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ydbio.2011.01.038"xsd:string |
| http://purl.uniprot.org/citations/21300049 | http://purl.uniprot.org/core/author | "Ito J."xsd:string |
| http://purl.uniprot.org/citations/21300049 | http://purl.uniprot.org/core/author | "Kageyama R."xsd:string |
| http://purl.uniprot.org/citations/21300049 | http://purl.uniprot.org/core/author | "Imayoshi I."xsd:string |
| http://purl.uniprot.org/citations/21300049 | http://purl.uniprot.org/core/author | "Tateya I."xsd:string |
| http://purl.uniprot.org/citations/21300049 | http://purl.uniprot.org/core/author | "Tateya T."xsd:string |
| http://purl.uniprot.org/citations/21300049 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21300049 | http://purl.uniprot.org/core/name | "Dev Biol"xsd:string |
| http://purl.uniprot.org/citations/21300049 | http://purl.uniprot.org/core/pages | "329-340"xsd:string |
| http://purl.uniprot.org/citations/21300049 | http://purl.uniprot.org/core/title | "Cooperative functions of Hes/Hey genes in auditory hair cell and supporting cell development."xsd:string |
| http://purl.uniprot.org/citations/21300049 | http://purl.uniprot.org/core/volume | "352"xsd:string |
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