ZFIN ID: ZDB-PUB-001220-6
Distinct requirements for zebrafish angiogenesis revealed by a VEGF-A morphant
Nasevicius, A., Larson, J., and Ekker, S.C.
Date: 2000
Source: Yeast (Chichester, England)   17(4): 294-301 (Journal)
Registered Authors: Ekker, Stephen C., Larson, Jon D., Nasevicius, Aidas
Keywords: zebrafish; VEGF-A; fli-1; flk-1; angiogenesis; vasculature; morpholino; morphant
MeSH Terms:
  • Animals
  • Blood Vessels/embryology*
  • Body Patterning
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism
  • Embryonic Development
  • Endothelial Growth Factors/genetics*
  • Endothelial Growth Factors/physiology*
  • Gene Expression
  • Gene Targeting*
  • Morpholines
  • Mutation
  • Neovascularization, Physiologic*
  • Oligonucleotides, Antisense
  • Phenotype
  • Proto-Oncogene Protein c-fli-1
  • Proto-Oncogene Proteins*
  • Receptor Protein-Tyrosine Kinases/genetics
  • Receptor Protein-Tyrosine Kinases/metabolism
  • Receptors, Growth Factor/genetics
  • Receptors, Growth Factor/metabolism
  • Receptors, Vascular Endothelial Growth Factor
  • Signal Transduction
  • Trans-Activators/genetics
  • Trans-Activators/metabolism
  • Vascular Endothelial Growth Factor A
  • Zebrafish/embryology*
  • Zebrafish/genetics*
PubMed: 11119306 Full text @ Yeast
Angiogenesis is a fundamental vertebrate developmental process that requires signalling by the secreted protein vascular endothelial growth factor-A (VEGF-A). VEGF-A functions in the development of embryonic structures, during tissue remodelling and for the growth of tumour-induced vasculature. The study of the role of VEGF-A during normal development has been significantly complicated by the dominant, haplo-insufficient nature of VEGF-A-targeted mutations in mice. We have used morpholino-based targeted gene knock-down technology to generate a zebrafish VEGF-A morphant loss of function model. Zebrafish VEGF-A morphant embryos develop with an enlarged pericardium and with major blood vessel deficiencies. Morphological assessment at 2 days of development indicates a nearly complete absence of both axial and intersegmental vasculature, with no or reduced numbers of circulating red blood cells. Molecular analysis using the endothelial markers fli-1 and flk-1 at 1 day of development demonstrates a fundamental distinction between VEGF-A requirements for axial and intersegmental vascular structure specification. VEGF-A is not required for the initial establishment of axial vasculature patterning, whereas all development of intersegmental vasculature is dependent on VEGF-A signalling. The zebrafish thus serves as a quality model for the study of conserved vertebrate angiogenesis processes during embryonic development.