Stimulation of regenerative blastema formation in lizards as a model to analyze limb regeneration in amniotes

Abstract

The hypothesis here presented tries to explain why organ regeneration is present in fish and amphibians (anamniotes) but is absent in reptiles, birds and mammals (amniotes). Anamniotes possess complex life cycles including larvae and metamorphosis stages, the latter representing a physiological form of organ destruction and regeneration coded in their genome that can be reactivated in adults in the form of regeneration. Part of the genome for larvae and metamorphosis phases was likely lost in amniotes with the evolution of direct development, the potentiation of the immune system and the increase in complexity of the nervous system. These events consequently determined incapability for organ regeneration in extant amniotes with the exception of the lizard tail. This likely derives from the evolution of a mechanism of immunosuppression that allows the regeneration of the tail although the complete morphogenetic plane of tail embryogenesis is lost. The lizard model of imperfect but outstanding organ regeneration indicates the possibility to improve organ regeneration also in other amniotes. In fact, the induction of a blastema in the amputated lizard limb has stimulated the formation of short limbs containing cartilaginous bones of the femur, tibia and fibula, and these experiments foster some hope for future attempts to induce limb and digit regeneration also in mammals.