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Title

The RNA binding protein Zfp36l1 is required for normal vascularisation and post-transcriptionally regulates VEGF expression

AuthorsBell, Sarah E.; Sánchez, María José ; Spasic-Boskovic, Olivera; Santalucía, Tomàs ; Gambardella, Laure; Burton, Graham J.; Murphy, John J.; Norton, John D.; Clark, Andrew R.; Turner, Martin
KeywordsZfp36I1
VEGF
Extraembryonic and intraembryonic vasculature
Neovascularization
Nuclear proteins
Polyribosomes
Vascular Endothelial Growth Factor A
Mutation
Issue Date29-Sep-2006
PublisherWiley-Liss
CitationDevelopmental Dynamics 235(11): 3144-3155 (2006)
AbstractThe Zfp36l1 gene encodes a zinc finger-containing mRNA binding protein implicated in the posttranscriptional control of gene expression. Mouse embryos homozygous for a targeted mutation in the Zfp36l1 locus died mid-gestation and exhibited extraembryonic and intraembryonic vascular abnormalities and heart defects. In the developing placenta, there was a failure of the extraembryonic mesoderm to invaginate the trophoblast layer. The phenotype was associated with an elevated expression of vascular endothelial growth factor (VEGF)-A in the embryos and in embryonic fibroblasts cultured under conditions of both normoxia and hypoxia. VEGF-A overproduction by embryonic fibroblasts was not a consequence of changes in Vegf-a mRNA stability; instead, we observed enhanced association with polyribosomes, suggesting Zfp36l1 influences translational regulation. These data implicate Zfp36l1as a negative regulator of Vegf-a gene activity during development.
Description12 páginas, 9 figuras, 1 tabla.
Publisher version (URL)http://dx.doi.org/10.1002/dvdy.20949
URIhttp://hdl.handle.net/10261/41396
DOI10.1002/dvdy.20949
ISSN1058-8388
E-ISSN1097-0177
Appears in Collections:(CABD) Artículos
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