PUBLICATION
Dissection of angiogenic signaling in zebrafish using a chemical genetic approach
- Authors
- Chan, J., Bayliss, P.E., Wood, J.M., and Roberts, T.M.
- ID
- ZDB-PUB-020423-2
- 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
Citation
Chan, J., Bayliss, P.E., Wood, J.M., and Roberts, T.M. (2002) Dissection of angiogenic signaling in zebrafish using a chemical genetic approach. Cancer Cell. 1(3):257-267.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping