Distinct requirements for zebrafish angiogenesis revealed by a VEGF-A morphant

Aidas Nasevicius, Jon Larson, Stephen G. Ekker

Research output: Contribution to journalArticlepeer-review

204 Scopus citations


Angiogcnesis is a fundamental vertebrate developmental process that requires signalling by the secreted protein vascular cndothclial 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 interscgmcntal 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.

Original languageEnglish (US)
Pages (from-to)294-301
Number of pages8
Issue number4
StatePublished - 2000


  • Angiogenesis
  • Fli-1
  • Flk-1
  • Morphant
  • Morpholino
  • VEGF-A
  • Vasculature
  • Zebrafish

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Genetics


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