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Dev Dyn. 2006 Nov;235(11):3144-55.

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

Author information

1
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Babraham, Cambridge, United Kingdom. sarah-e.bell@bbsrc.ac.uk

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.

PMID:
17013884
DOI:
10.1002/dvdy.20949
[Indexed for MEDLINE]
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