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Updated: May 16, 2026
09:04
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
VEGF/Flk1 signaling cascade transactivates Etv2 gene expression
Tara L Rasmussen1, Xiaozhong Shi, Alicia Wallis
1Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota, United States of America.
Plos One
|November 28, 2012
Summary
Vascular Endothelial Growth Factor (VEGF) activates Etv2 expression through Flk1 signaling. This pathway involves p38 MAPK and Creb, clarifying the genetic hierarchy in early development.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- The precise genetic relationship between Ets related protein 71 (Er71/Etv2) and Flk1 in early development remains incompletely understood.
- Clarifying this hierarchy is crucial for understanding vascular development and related cellular processes.
Purpose of the Study:
- To genetically define the molecular cascade and upstream regulators of Etv2 expression.
- To investigate the role of Flk1 signaling in the activation of Etv2 during embryonic development.
Main Methods:
- Utilized Etv2-EYFP reporter mice to track Etv2 expression patterns relative to Flk1.
- Analyzed gene expression in Flk1 and Etv2 mutant mouse models.
- Performed transcriptional assays, pharmacological inhibition, EMSA, and ChIP assays to elucidate signaling pathways.
Main Results:
- Flk1 is confirmed to be upstream of Etv2 during gastrulation, with Etv2 expressed in a subset of Flk1-positive cells.
- VEGF activates the Etv2 promoter via Flk1 signaling, dependent on p38 MAPK and subsequent Creb activation.
- Identified a specific VEGF response element in the Etv2 promoter bound by Creb.
Conclusions:
- VEGF signaling through Flk1 is essential for Etv2 expression.
- The p38 MAPK/Creb pathway mediates VEGF-induced Etv2 activation.
- This study establishes a clear molecular cascade linking VEGF/Flk1 signaling to Etv2 regulation.
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