ZFIN ID: ZDB-PUB-170115-4
Vegfd modulates both angiogenesis and lymphangiogenesis during zebrafish embryonic development
Bower, N.I., Vogrin, A.J., Le Guen, L., Chen, H., Stacker, S.A., Achen, M.G., Hogan, B.M.
Date: 2017
Source: Development (Cambridge, England)   144(3): 507-518 (Journal)
Registered Authors: Hogan, Ben M., Le Guen, Ludovic
Keywords: Flt4, Kdr, Lymphangiogenesis, Lymphatic, Vegfc, Vegfd
MeSH Terms:
  • Animals
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/physiology
  • Lymphangiogenesis/genetics
  • Lymphangiogenesis/physiology*
  • Membrane Proteins/genetics
  • Membrane Proteins/physiology
  • Models, Biological
  • Mutagenesis
  • Neovascularization, Physiologic/genetics
  • Neovascularization, Physiologic/physiology*
  • Sequence Deletion
  • Signal Transduction
  • Up-Regulation
  • Vascular Endothelial Growth Factor C/genetics
  • Vascular Endothelial Growth Factor C/physiology
  • Vascular Endothelial Growth Factor D/genetics
  • Vascular Endothelial Growth Factor D/physiology*
  • Vascular Endothelial Growth Factor Receptor-1/genetics
  • Vascular Endothelial Growth Factor Receptor-1/physiology
  • Vascular Endothelial Growth Factor Receptor-2/genetics
  • Vascular Endothelial Growth Factor Receptor-2/physiology
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed: 28087639 Full text @ Development
Vascular endothelial growth factors (VEGFs) control angiogenesis and lymphangiogenesis during development and in pathological conditions. In the zebrafish trunk, Vegfa controls the formation of intersegmental arteries by primary angiogenesis and Vegfc is essential for secondary angiogenesis, the formation of veins and lymphatics. VEGFD has been largely thought of as dispensable for vascular development in vertebrates. Here, we generated a zebrafish vegfd mutant by genome editing. vegfd mutants display significant defects in facial lymphangiogenesis independent of vegfc function. Strikingly, we find that vegfc and vegfd cooperatively control lymphangiogenesis throughout the embryo, including during the formation of the trunk lymphatic vasculature. Interestingly, we find that vegfd and vegfc also redundantly drive artery hyperbranching phenotypes observed upon depletion of Flt1 or Dll4. Epistasis and biochemical binding assays suggest that during primary angiogenesis Vegfd influences these phenotypes through Kdr (Vegfr2) rather than Flt4 (Vegfr3). These data demonstrate that, rather than being dispensable during development, Vegfd plays context specific indispensible and also compensatory roles during both blood vessel angiogenesis and lymphangiogenesis.