Format

Send to

Choose Destination
See comment in PubMed Commons below
Cancer Cell. 2002 Apr;1(3):257-67.

Dissection of angiogenic signaling in zebrafish using a chemical genetic approach.

Author information

1
Department of Cancer Biology, Dana-Farber Cancer Institute and the Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA. jochan@mbcrr.harvard.edu

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.

PMID:
12086862
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center