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The Wilms’ tumor transcription factor WT1 regulates expression of the VE‐cadherin gene
Author(s) -
Kirschner Karin Michaela,
Scholz Holger
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.925.16
Subject(s) - biology , transcription factor , gata6 , gene , cadherin , microbiology and biotechnology , reporter gene , zinc finger transcription factor , gene expression , cancer research , cell , zinc finger , genetics
The Wilms’ tumor transcription factor, WT1, is an important regulator of embryonic development. A predominant feature of Wt1‐deficient mouse embryos is their lack of kidneys and gonads in addition to a failure of normal formation of the vasculature in the heart. Identification of downstream target genes is necessary to understand the function of WT1 during normal embryogenesis. Here we demonstrate, that WT1 stimulates expression of the vascular endothelial (VE) cadherin gene. VE‐cadherin transcripts were increased more then 15‐fold in a cell line with inducible WT1 expression. WT1 enhanced VE‐cadherin expression also at the protein level in these cells. With the combinatorial use of luciferase reporter gene assays and electrophoretic mobility shift experiments we identified cis‐regulatory elements in the promoter and the first intron of the VE‐cadherin gene. Activation of the reporter constructs by WT1 was abolished upon introducing mutations into the identified binding sites. Immunohistochemical staining revealed co‐expression of WT1 and VE‐cadherin in the developing glomeruli of normal kidneys. VE‐cadherin expression was significantly reduced in the hearts and livers of Wt1‐deficient mouse embryos. These findings indicate that WT1 stimulates transcription of the VE‐cadherin gene, which, in turn, may promote vascular endothelial cell survival through stabilization of cell‐cell contacts.