Chemical modulation of receptor signaling inhibits regenerative angiogenesis in adult zebrafish.
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 Cgamma1, 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.
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Peter E
PE
Bayliss
Kimberly L
KL
Bellavance
Geoffrey G
GG
Whitehead
Joshua M
JM
Abrams
Sandrine
S
Aegerter
Heather S
HS
Robbins
Douglas B
DB
Cowan
Mark T
MT
Keating
Terence
T
O'Reilly
Jeanette M
JM
Wood
Thomas M
TM
Roberts
Joanne
J
Chan
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D048091:Guided Tissue Regeneration / Q000379:methods; D006579:Heterozygote; D008856:Microscopy, Fluorescence; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D051966:Phospholipase C gamma / Q000494:pharmacology; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D012879:Skin Physiological Phenomena / Q000187:drug effects; D023822:Tissue Engineering; D015027:Zebrafish / Q000502:physiology*
D020533:Angiogenesis Inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor; D051966:Phospholipase C gamma