|ZFIN ID: ZDB-PUB-020423-2|
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Dissection of angiogenic signaling in zebrafish using a chemical genetic approach
Chan, J., Bayliss, P.E., Wood, J.M., and Roberts, T.M.
|Source:||Cancer Cell 1(3): 257-267 (Journal)|
|Registered Authors:||Bayliss, Peter, Chan, Joanne, Roberts, Thomas M.|
|PubMed:||12086862 Full text @ Cancer Cell|
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.
ABSTRACTStriking 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.