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 Writ 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. (C) 2008 Elsevier Inc. All rights reserved.