Perspective: Appendage regeneration in amphibians and some reptiles derived from specific evolutionary histories.

Some hypotheses on the evolution of regeneration in amphibians and reptiles are presented. Amphibian regeneration is derived from metamorphosis present in sarcopterygian fish and amphibians of the Devonian-Carboniferous. The genetic ability to rebuild organs during metamorphosis was maintained in form of "regeneration" in urodele and anuran tadpoles. Amphibian regeneration may be a consequence of the transition from an aquatic to a terrestrial environment through the evolution of a developmental program for the tadpole stage and replacements of adult organs controlled by the endocrine and immune system. Following metamorphosis, the regeneration program for terrestrial anurans and amniotes was lost or modified, whereas the immune system involved in self-integrity and microbial protection became in charge of regeneration that was replaced by scarring. Among amniotes only lizards regenerate an organ as large and complex as the tail. It is hypothesized that in Permian captorhinids and in Triassic lizards (eosuchians) a regenerative blastema evolved in relation to autotomy, a unique phenomenon present in these reptiles that enhanced survival against the larger predators of the Permian-Mesozoic. Appendage regeneration in amphibians and lizards occurs after the migration of activated mesenchymal and epidermal cells in the wounded areas to form soft and hyaluronate-rich blastemas. Autotomy and production of high hyaluronate levels allows high hydration and immunosuppression, favoring regeneration. It is suggested that a way for regenerative medicine to induce limb regeneration in humans is to develop medical procedures to recreate soft blastemas that can grow, a long and difficult process because it counteracts mammalian evolution toward scarring.