2006
DOI: 10.1038/nchembio778
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Chemical modulation of receptor signaling inhibits regenerative angiogenesis in adult zebrafish

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 smallmolecule 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 dir… Show more

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Cited by 131 publications
(139 citation statements)
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“…S7 C and D). Importantly, the loss of VEGFR1 does not reduce β-catenin, and VEGFR inhibitors block the regenerative angiogenesis but not tailfin regrowth in zebrafish (28,29), suggesting that axitinib inhibits Wnt signaling independently of VEGFRs in vitro and in vivo.…”
Section: Resultsmentioning
confidence: 99%
“…S7 C and D). Importantly, the loss of VEGFR1 does not reduce β-catenin, and VEGFR inhibitors block the regenerative angiogenesis but not tailfin regrowth in zebrafish (28,29), suggesting that axitinib inhibits Wnt signaling independently of VEGFRs in vitro and in vivo.…”
Section: Resultsmentioning
confidence: 99%
“…Elevation of vascularization resulting in early regeneration was documented in several animals, e.g., in mice a drastic amount of microvascularization was observed, which triggers the entire regeneration of partial hepatectomic liver (Drixler et al, 2002). Likewise, it plays a significant role in the regeneration of fins in zebrafish (Bayliss et al, 2006) and blastema development of newts (Rageh et al, 2002). Differentiation and pattern formation are the major processes in early development and organogenesis.…”
Section: Discussionmentioning
confidence: 99%
“…Fadrozole was dissolved in system water at 50 μg/l (Ankley et al, 2002;Zhang et al, 2009). PTK787 (Selleck Chemicals) was dissolved in system water at an effective final concentration of 500 nM (Bayliss et al, 2006). Zebrafish were kept in glass tanks throughout treatments.…”
Section: Chemical Treatmentsmentioning
confidence: 99%
“…To determine whether an additional blood vessel network is required for BT formation, Tg(KR21; fli1a:EGFP) females were treated with T (1 μg/l) and PTK787 (500 nM), an inhibitor of vascular endothelial growth factor receptor tyrosine kinases that effectively inhibits regenerative angiogenesis in the zebrafish caudal fin (Wood et al, 2000;Bayliss et al, 2006). Immediately following pectoral fin amputation, PTK787 treatments were initiated.…”
Section: Bt Cluster Formation Depends On the Development Of An Additimentioning
confidence: 99%