Bayliss Peter E, Bellavance Kimberly L, Whitehead Geoffrey G, Abrams Joshua M, Aegerter Sandrine, Robbins Heather S, Cowan Douglas B, Keating Mark T, O'Reilly Terence, Wood Jeanette M, Roberts Thomas M, Chan Joanne
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nat Chem Biol. 2006 May;2(5):265-73. doi: 10.1038/nchembio778. Epub 2006 Mar 26.
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.
我们利用化学方法抑制成年斑马鱼尾鳍中的血管内皮生长因子受体，研究了血管生成的作用以及受体信号传导的必要性。通过使用小分子抑制剂，我们能够对血管再生进行精确控制。确定了组织再生的血管生成极限，因为含有皮肤、色素、神经轴突和骨前体细胞的无血管组织最多可再生约1毫米。这表明组织可以在不与内皮细胞直接相互作用且远离血液供应的情况下再生。我们还研究了在斑马鱼血管突变体中化学抑制的效果是否可以增强。我们发现，关键受体效应物磷脂酶Cγ1发生突变的成年杂合斑马鱼对化学抑制表现出更高的敏感性。这项研究说明了成年斑马鱼作为受体信号传导和化学生物学新模型系统的实用性。
