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

Sarah E. Bell, Maria Jose Sanchez, Olivera Spasic-Boskovic, Tomas Santalucia, Laure Gambardella, Graham J. Burton, John J. Murphy, John D. Norton, Andrew R. Clark, Martin Turner

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3144-3155
Number of pages12
JournalDevelopmental Dynamics
Volume235
Issue number11
DOIs
Publication statusPublished - 1 Nov 2006

Keywords

  • Extraembryonic and intraembryonic vasculature
  • VEGF
  • Zfp36l1

ASJC Scopus subject areas

  • Developmental Biology

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