Tgf-β superfamily and limb regeneration: Tgf-β to start and Bmp to end

Axolotls represent a popular model to study how nature solved the problem of regenerating lost appendages in tetrapods. Our work over many years focused on trying to understand how these animals can achieve such a feat and not end up with a scarred up stump. The Tgf-β superfamily represents an interesting family to target since they are involved in wound healing in adults and pattern formation during development. This family is large and comprises Tgf-β, Bmps, activins and GDFs. In this review, we present work from us and others on Tgf-β & Bmps and highlight interesting observations between these two sub-families. Tgf-β is important for the preparation phase of regeneration and Bmps for the redevelopment phase and they do not overlap with one another. We present novel data showing that the Tgf-β non-canonical pathway is also not active during redevelopment. Finally, we propose a molecular model to explain how Tgf-β and Bmps maintain distinct windows of expression during regeneration in axolotls.