The transcriptional repressor CDP (Cutl1) is essential for epithelial cell differentiation of the lung and the hair follicle

Details

Serval ID
serval:BIB_639E69B3B68B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The transcriptional repressor CDP (Cutl1) is essential for epithelial cell differentiation of the lung and the hair follicle
Journal
Genes and Development
Author(s)
Ellis  T., Gambardella  L., Horcher  M., Tschanz  S., Capol  J., Bertram  P., Jochum  W., Barrandon  Y., Busslinger  M.
ISSN
0890-9369 (Print)
Publication state
Published
Issued date
09/2001
Volume
15
Number
17
Pages
2307-19
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep 1
Abstract
The mammalian Cutl1 gene codes for the CCAAT displacement protein (CDP), which has been implicated as a transcriptional repressor in diverse processes such as terminal differentiation, cell cycle progression, and the control of nuclear matrix attachment regions. To investigate the in vivo function of Cutl1, we have replaced the C-terminal Cut repeat 3 and homeodomain exons with an in-frame lacZ gene by targeted mutagenesis in the mouse. The CDP-lacZ fusion protein is retained in the cytoplasm and fails to repress gene transcription, indicating that the Cutl1(lacZ) allele corresponds to a null mutation. Cutl1 mutant mice on inbred genetic backgrounds are born at Mendelian frequency, but die shortly after birth because of retarded differentiation of the lung epithelia, which indicates an essential role of CDP in lung maturation. A less pronounced delay in lung development allows Cutl1 mutant mice on an outbred background to survive beyond birth. These mice are growth-retarded and develop an abnormal pelage because of disrupted hair follicle morphogenesis. The inner root sheath (IRS) is reduced, and the transcription of Sonic hedgehog and IRS-specific genes is deregulated in Cutl1 mutant hair follicles, consistent with the specific expression of Cutl1 in the progenitors and cell lineages of the IRS. These data implicate CDP in cell-lineage specification during hair follicle morphogenesis, which resembles the role of the related Cut protein in specifying cell fates during Drosophila development.
Keywords
Alleles Animals Cell Differentiation Cytoplasm/metabolism DNA, Complementary/metabolism Drosophila Epithelial Cells/*metabolism Exons Gene Expression Regulation, Developmental Hair/embryology Hedgehog Proteins Homeodomain Proteins Immunohistochemistry In Situ Hybridization Lung/*cytology/embryology/pathology Mice Models, Genetic Molecular Sequence Data Mutagenesis, Site-Directed Mutation Nuclear Proteins/*physiology Protein Structure, Tertiary Repressor Proteins/*physiology Time Factors Trans-Activators/metabolism Transcription, Genetic Transfection beta-Galactosidase/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 8:41
Last modification date
20/08/2019 14:20
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