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

Dev Dyn. 2006 Nov;235(11):3144-55. doi: 10.1002/dvdy.20949.

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 Zfp36l1as a negative regulator of Vegf-a gene activity during development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butyrate Response Factor 1
  • Gene Expression Regulation, Developmental*
  • Mice
  • Mice, Mutant Strains
  • Mutation
  • Neovascularization, Physiologic / genetics*
  • Nuclear Proteins / analysis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Polyribosomes / metabolism
  • RNA Stability
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / analysis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / physiology*
  • Transcription, Genetic
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Butyrate Response Factor 1
  • Nuclear Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Vascular Endothelial Growth Factor A
  • Zfp36l1 protein, mouse