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ZFIN ID: ZDB-PUB-020423-2
Dissection of angiogenic signaling in zebrafish using a chemical genetic approach
Chan, J., Bayliss, P.E., Wood, J.M., and Roberts, T.M.
Date: 2002
Source: Cancer Cell   1(3): 257-267 (Journal)
Registered Authors: Bayliss, Peter, Chan, Joanne, Roberts, Thomas M.
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Angiogenesis Inhibitors/pharmacology
  • Animals
  • DNA, Complementary
  • Embryo, Nonmammalian/blood supply*
  • Endothelium, Vascular/cytology
  • Enzyme Inhibitors/pharmacology
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Molecular Sequence Data
  • Neovascularization, Physiologic/physiology*
  • Phthalazines/pharmacology
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins/metabolism
  • Proto-Oncogene Proteins c-akt
  • Pyridines*
  • RNA/metabolism
  • Receptor Protein-Tyrosine Kinases/antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases/metabolism
  • Receptors, Growth Factor/antagonists & inhibitors
  • Receptors, Growth Factor/metabolism
  • Receptors, Vascular Endothelial Growth Factor
  • Sequence Homology, Amino Acid
  • Signal Transduction/physiology*
  • Up-Regulation
  • Zebrafish/embryology*
PubMed: 12086862 Full text @ Cancer Cell
Striking homology between signaling molecules in zebrafish and humans suggests that compounds known to inhibit human kinases may enable a chemical genetic approach to dissect signaling pathways in the zebrafish embryo. We tested this hypothesis using a vascular endothelial growth factor receptor inhibitor, PTK787/ZK222584. Zebrafish embryos treated with this compound lacked all major blood vessels. Overexpression of AKT/PKB, a putative effector of vascular endothelial growth factor signaling, allowed blood vessels to form in the presence of drug. Endothelial cell apoptosis induced by the drug is prevented by increasing AKT/PKB activity, thus establishing the physiological relevance of AKT/PKB in the angiogenic process. This approach allowed us to examine the effects of blood flow and the role of endothelial signals in organogenesis.