The product of the mouse nude locus, Whn, regulates the balance between epithelial cell growth and differentiation.

Details

Serval ID
serval:BIB_C5256576CBCA
Type
Article: article from journal or magazin.
Collection
Publications
Title
The product of the mouse nude locus, Whn, regulates the balance between epithelial cell growth and differentiation.
Journal
Genes and Development
Author(s)
Brissette J.L., Li J., Kamimura J., Lee D., Dotto G.P.
ISSN
0890-9369 (Print)
ISSN-L
0890-9369
Publication state
Published
Issued date
1996
Volume
10
Number
17
Pages
2212-2221
Language
english
Notes
Publication types: Journal Article ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Abstract
Mutations in the winged-helix nude (whn) gene result in the nude mouse and rat phenotypes. The pleiotropic nude phenotype which affects the hair, skin, and thymus suggests that whn plays a pivotal role in the development and/or maintenance of these organs. However, little is known about whn function in these organs. We show here that in skin whn is specifically expressed in epithelial cells and not the mesenchymal cells, and using a hair reconstitution assay, we demonstrate that the abnormal nude mouse hair development is attributable to a functional defect of the epithelial cells. Examination of nude mouse primary keratinocytes in culture revealed that these cells have an increased propensity to differentiate in an abnormal fashion, even under conditions that promote proliferation. Furthermore, nude mouse keratinocytes displayed a 100-fold increased sensitivity to the growth-inhibitory/differentiation effects of the phorbol ester TPA. In parallel with these findings, we directly show that whn functions as a transcription factor that can specifically suppress expression of differentiation/TPA-responsive genes. The region of Whn responsible for these effects was mapped to the carboxy-terminal transactivating domain. These results establish whn as a key regulatory factor involved in maintaining the balance between keratinocyte growth and differentiation. The general implications of these findings for an epithelial self-renewal model will be discussed.
Keywords
Animals, Blotting, Northern, Cells, Cultured, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Epithelium/growth & development, Forkhead Transcription Factors, Gene Expression Regulation, Developmental, Hair/metabolism, Immunoblotting, Keratinocytes/drug effects, Keratinocytes/metabolism, Mice, Mice, Nude/genetics, Mice, Nude/metabolism, Phorbol Esters/adverse effects, Plasmids, Promoter Regions, Genetic/physiology, Skin/cytology, Skin/growth & development, Transcription Factors/genetics, Transcription Factors/metabolism, Transcription, Genetic, Transfection
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:58
Last modification date
20/08/2019 16:40
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