Lin Gufa, Slack Jonathan M W
Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
Dev Biol. 2008 Apr 15;316(2):323-35. doi: 10.1016/j.ydbio.2008.01.032. Epub 2008 Feb 7.
We have investigated the requirement for the FGF and Wnt/beta-catenin pathways for Xenopus tadpole tail regeneration. Pathways were modified either by treatment with small molecules or by induction of transgene expression with heat shocks. Regeneration is inhibited by treatment with the FGF inhibitor SU5402, or by activation of a dominant negative FGF receptor, or by activation of expression of the Wnt inhibitor Dkk1. Agents promoting Wnt activity: the small molecule BIO, or a constitutively active form of beta-catenin, led to an increased growth rate. Combination of a Wnt activator with FGF inhibitor suppressed regeneration, while combination of a Wnt inhibitor with a FGF activator allowed regeneration. This suggests that the Wnt activity lies upstream of the FGF activity. Expression of both Wnt and FGF components was inhibited by activation of noggin, suggesting that BMP signalling lies upstream of both Wnt and FGF. The results show that the molecular mechanism of Xenopus tadpole tail regeneration is surprisingly similar to that of the Xenopus limb bud and the zebrafish caudal fin, despite the difference of anatomy.
我们研究了非洲爪蟾蝌蚪尾巴再生对成纤维细胞生长因子（FGF）和Wnt/β-连环蛋白信号通路的需求。通过用小分子处理或热休克诱导转基因表达来改变信号通路。用FGF抑制剂SU5402处理、激活显性负性FGF受体或激活Wnt抑制剂Dkk1的表达均可抑制再生。促进Wnt活性的试剂：小分子BIO或β-连环蛋白的组成型活性形式，导致生长速率增加。Wnt激活剂与FGF抑制剂的组合抑制再生，而Wnt抑制剂与FGF激活剂的组合则允许再生。这表明Wnt活性位于FGF活性的上游。头蛋白（noggin）的激活抑制了Wnt和FGF成分的表达，表明骨形态发生蛋白（BMP）信号传导位于Wnt和FGF两者的上游。结果表明，尽管解剖结构不同，但非洲爪蟾蝌蚪尾巴再生的分子机制与非洲爪蟾肢体芽和斑马鱼尾鳍的分子机制惊人地相似。
