Abstract

We examined the role of angiogenesis and the need for receptor signaling using chemical inhibition of the vascular endothelial growth factor receptor in the adult zebrafish tail fin. Using a small-molecule inhibitor, we were able to exert precise control over blood vessel regeneration. An angiogenic limit to tissue regeneration was determined, as avascular tissue containing skin, pigment, neuronal axons and bone precursors could regenerate up to about 1 mm. This indicates that tissues can regenerate without direct interaction with endothelial cells and at a distance from blood supply. We also investigated whether the effects of chemical inhibition could be enhanced in zebrafish vascular mutants. We found that adult zebrafish, heterozygous for a mutation in the critical receptor effector phospholipase C1, show a greater sensitivity to chemical inhibition. This study illustrates the utility of the adult zebrafish as a new model system for receptor signaling and chemical biology.

1. Department of Cancer Biology, Dana-Farber Cancer Institute and the Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
2. Vascular Biology Program, Children's Hospital and the Department of Surgery, Harvard Medical School, Boston, Massachusetts 02115, USA.
3. Department of Cardiology, Children's Hospital, Howard Hughes Medical Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
4. Department of Anesthesia, Harvard Medical School and Children's Hospital, Boston, Massachusetts 02115, USA.
5. Oncology Research, Novartis Pharma AG, CH-4002 Basel, Switzerland.
6. These authors contributed equally to this work.

Correspondence to: Joanne Chan² e-mail: joanne.chan@childrens.harvard.edu

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