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Title: Cooperative functions of Hes/Hey genes in auditory hair cell and supporting cell development.
Authors: Tateya, Tomoko  kyouindb  KAKEN_id
Imayoshi, Itaru  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-9728-481X (unconfirmed)
Tateya, Ichiro  kyouindb  KAKEN_id
Ito, Juichi  KAKEN_id
Kageyama, Ryoichiro  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-5985-1120 (unconfirmed)
Author's alias: 影山, 龍一郎
Keywords: Hair cell
Supporting cell
Hes1
Hes5
Hey1
Developing cochlea
Issue Date: 15-Apr-2011
Publisher: Elsevier Inc.
Journal title: Developmental biology
Volume: 352
Issue: 2
Start page: 329
End page: 340
Abstract: 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.
Rights: © 2011 Elsevier Inc.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/158370
DOI(Published Version): 10.1016/j.ydbio.2011.01.038
PubMed ID: 21300049
Appears in Collections:Journal Articles

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