Regeneration: Growth Factors in Limb Regeneration

The remarkable phenomenon of limb regeneration in vertebrates is limited to some, but not all, amphibians. Despite this, it is widely believed that the ancestor of all vertebrates was capable of limb regeneration, suggesting that this ability could be reawakened in humans. Research into limb regeneration has benefited from the use of two complementary model systems. The urodele amphibians (newts and salamanders) can regenerate perfect limbs even as adults, initiating a programme of wound healing, blastema formation and redevelopment. Urodeles can be used to investigate how common wound-healing processes can subsequently activate a regeneration programme. Anuran amphibians (frogs and toads), on the other hand, progressively lose the ability to regenerate as they progress through their life cycle, and can be used in gain of function experiments to test potential regeneration factors. Using both of these models, growth factor signalling pathways have been identified as being involved in regulating all stages of the limb regeneration process. Key Concepts Regeneration of the limb is perfect in urodeles (newts and salamanders), declines with age in frogs and is absent in mammals. Urodele regeneration is divided into three distinct phases, wound healing, blastema formation and redevelopment. Mechanisms unique to regeneration are likely to be involved in the transition from phase I to phase II. Growth factors are important in regulating all three phases of limb regeneration. Amphibians are good models for studying the role of growth factors in limb regeneration, as both loss and gain of function experiments can be performed. Keywords: regeneration; growth factors; blastema; axolotl, Xenopus