Clec14a genetically interacts with Etv2 and Vegf signaling during vasculogenesis and angiogenesis in zebrafish
- Pociute, K., Schumacher, J.A., Sumanas, S.
- BMC Developmental Biology 19: 6 (Journal)
- Registered Authors
- Schumacher, Jennifer, Sumanas, Saulius
- Angiogenesis, Clec14, Etsrp, Vascular endothelial, Vasculogenesis, Vegf, Zebrafish, etv2
- MeSH Terms
- Animals, Genetically Modified
- Cell Differentiation/genetics
- Gene Expression Regulation, Developmental/genetics*
- Gene Knockout Techniques
- Neovascularization, Physiologic/genetics
- Neovascularization, Physiologic/physiology*
- Signal Transduction/genetics
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- 30953479 Full text @ BMC Dev. Biol.
Pociute, K., Schumacher, J.A., Sumanas, S. (2019) Clec14a genetically interacts with Etv2 and Vegf signaling during vasculogenesis and angiogenesis in zebrafish. BMC Developmental Biology. 19:6.
Background C-lectin family 14 Member A (Clec14a) is a transmembrane protein specifically expressed in vascular endothelial cells during embryogenesis. Previous in vitro and in vivo studies have provided conflicting data regarding Clec14a role in promoting or inhibiting angiogenesis, therefore its functional role in vascular development remains poorly understood.
Results Here we have generated a novel clec14a mutant allele in zebrafish embryos using TALEN genome editing. clec14a mutant embryos exhibit partial defects and delay in the sprouting of intersegmental vessels. These defects in angiogenesis are greatly increased upon the knockdown of a structurally related C1qr protein. Furthermore, a partial knockdown of an ETS transcription factor Etv2 results in a synergistic effect with the clec14a mutation and inhibits expression of early vascular markers in endothelial progenitor cells, arguing that clec14a is involved in promoting vasculogenesis. In addition, Clec14a genetically interacts with Vegfa signaling. A partial knockdown of Vegfaa function in the clec14a mutant background resulted in a synergistic inhibition of intersegmental vessel sprouting.
Conclusions These results argue that clec14a is involved in both vasculogenesis and angiogenesis, and suggest that Clec14a genetically interacts with Etv2 and Vegf signaling during vascular development in zebrafish embryos.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes