ZFIN ID: ZDB-PUB-171019-22
Vegfa signaling regulates diverse artery/vein formation in vertebrate vasculatures
Jin, D., Zhu, D., Fang, Y., Chen, Y., Yu, G., Pan, W., Liu, D., Li, F., Zhong, T.P.
Date: 2017
Source: Journal of genetics and genomics = Yi chuan xue bao   44(10): 483-492 (Journal)
Registered Authors: Jin, Daqing, Liu, Dong, Pan, Weijun, Zhong, Tao P.
Keywords: Arterial-venous specification, TALEN, Vegfa, Zebrafish
MeSH Terms:
  • Alleles
  • Amino Acid Sequence
  • Animals
  • Arteries/embryology*
  • Base Sequence
  • Brain/blood supply
  • Brain/embryology
  • Embryonic Development
  • Mutation
  • Neovascularization, Physiologic*
  • Pseudopodia/metabolism
  • Signal Transduction*
  • Vascular Endothelial Growth Factor A/chemistry
  • Vascular Endothelial Growth Factor A/genetics
  • Vascular Endothelial Growth Factor A/metabolism*
  • Veins/embryology*
  • Zebrafish/embryology
  • Zebrafish/genetics
PubMed: 29037991 Full text @ J. Genet. Genomics
Vascular endothelial growth factor A (Vegfa) signaling regulates vascular development during embryogenesis and organ formation. However, the signaling mechanisms that govern the formation of various arteries/veins in various tissues are incompletely understood. In this study, we utilized transcription activator-like effector nuclease (TALEN) to generate zebrafish vegfaa mutants. vegfaa-/- embryos are embryonic lethal, and display a complete loss of the dorsal aorta (DA) and expansion of the cardinal vein. Activation of Vegfa signaling expands the arterial cell population at the expense of venous cells during vasculogenesis of the axial vessels in the trunk. Vegfa signaling regulates endothelial cell (EC) proliferation after arterial-venous specification. Vegfa deficiency and overexpression inhibit the formation of tip cell filopodia and interfere with the pathfinding of intersegmental vessels (ISVs). In the head vasculature, vegfaa‒/‒ causes loss of a pair of mesencephalic veins (MsVs) and central arteries (CtAs), both of which usually develop via sprouting angiogenesis. Our results indicate that Vegfa signaling induces the formation of the DA at the expense of the cardinal vein during the trunk vasculogenesis, and that Vegfa is required for the angiogenic formation of MsVs and CtAs in the brain. These findings suggest that Vegfa signaling governs the formation of diverse arteries/veins by distinct cellular mechanisms in vertebrate vasculatures.