Review. Limb regeneration in lizards under natural and experimental conditions with considerations on the induction of appendages regeneration in amniotes.

Abstract Background Study on the failure of limb regeneration in lizards evidences the difficult problems met from amniotes to regenerate organs. Contrary to the tail, limb loss in terrestrial environment is generally fatal and no selection for its regeneration occurred during lizard evolution. Methods Experimentally amputated limbs were fixed and embedded for microscopy. Results After limb loss an intense inflammatory reaction occurs and immune cells are recruited underneath a wound epidermis, forming a vascularized granulation tissue. The regenerating epidermis takes 2–3 weeks to cover the limb stump since degenerating long bones must be excised first while a dense connective tissue is formed and no limb growth occurs. Cell proliferation occurs in granulation tissues and wound epidermis during the initial 2–3 weeks of wound healing but disappears later determining the arrest of growth. Transcriptome data indicates that the limb, contrary to the tail, activates numerous genes involved in inflammation, immunity and fibroplasia while down-regulates some proliferative and most myogenic genes. Attempts to stimulate limb regeneration, by implants of nervous tissues or growth factors such as FGFs only maintain proliferation for few weeks but eventually the scarring program prevails and only short outgrowths missing of autopodial elements are regenerated. Conclusions While lizard limbs show the typical scarring outcome of mammals, the comparison of genes activated in the regenerating tail has allowed identifying key genes implicated in organ regeneration in amniotes.