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 (all 28) expand
PubMed: 11119306 Full text @ Yeast
ABSTRACT
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.
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