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The RNA binding protein Zfp36l1 is required for normal vascularisation and post‐transcriptionally regulates VEGF expression
Author(s) -
Bell Sarah E.,
Sanchez Maria Jose,
SpasicBoskovic Olivera,
Santalucia Tomas,
Gambardella Laure,
Burton Graham J.,
Murphy John J.,
Norton John D.,
Clark Andrew R.,
Turner Martin
Publication year - 2006
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20949
Subject(s) - biology , microbiology and biotechnology , messenger rna , embryonic stem cell , embryo , regulation of gene expression , gene expression , gene , genetics
The 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 Zfp36l1 as a negative regulator of Vegf‐a gene activity during development. Developmental Dynamics 235:3144–3155, 2006. © 2006 Wiley‐Liss, Inc.