Regeneration of complex structures is rare within amniotes. A well-known exception is the lizard tail. However, our knowledge on how this process is achieved at the cellular and molecular is very limited when compared to the regeneration of other appendages in another vertebrate groups. Moreover, and contrary to these last appendages the regenerated lizard tail although fully functional is not identical to the original one (for instance, the dorsal root ganglia flanking the central canal of the spinal cord are not regenerated, the scales are smaller and the skeletal muscle regenerates in a different organization). Now the laboratory of MK Vickaryous has revised the current knowledge on lizard tail regeneration, mainly focused on the blastema (http://onlinelibrary.wiley.com/doi/10.1002/reg2.31/abstract).

In many species the tail has a series of fracture planes that allow this appendage to be self-detached or autotomized mainly as defensive strategy. For the majority of lizards these fracture planes are intravertebral; however, many species can regenerate the tail if amputated outside these planes. After amputation a clot is formed distal to the original spinal cord. Just after 24 hours cells begin to proliferate at the wound and form a blastema. At the same time a wound epidermis is formed and proliferates becoming thicker and then referred as apical epithelial cap. As the blastema grows the ependymal tube from the original spinal cord also grows inside the blastema adjacent to the wound epithelium. Differentiation within the blastema appears to occur in a proximal to distal gradient.

Thus, lizard tail regeneration is clearly epimorphic with the formation of a wound epithelium and a blastema. As it happens for the amphibian limb the wound epithelium is essential for regeneration as its removal or prevention of formation inhibits tail regeneration. However, very little is known about the molecular interactions between the wound epithelium and the blastema. Concerning the blastema its cellular origin is mainly unknown. In light of what is known from the blastema of other appendages in amphibians and zebrafish, it seems probable that the lizard tail’s blastema will be formed also by lineage-restricted cells, although experimental confirmation is needed. After amputation several cell populations begin to proliferate within the blastema. As differentiation occurs, proliferation decreases although chondroblasts and myoblasts continue to proliferate until the tail is fully regenerated. The presence of resident/stem progenitor populations has been suggested for the skeletal muscle and ependymal tube, although their existence needs to be unambiguously confirmed.

During tail regeneration the ependymal tube seems to have a central role in the reestablishment of the primary axis. Thus, it organizes and guides unmyelinated tracts from the original tail and likely induces and directs the outgrowth of the new tail. In fact, the ependymal tube is one of the first structures that appear within the blastema (at 4 days). Importantly, if the spinal cord adjacent to the wound is ablated or blocked from outgrowing, regeneration is inhibited. What seems to be important here are the ependymal cells that line the central canal of the spinal cord. More amazingly, transplants of ependymal tube to ectopic locations can stimulate regeneration. Finally, the ependymal tube has been also suggested to have a central role on the patterning of the regenerated tail and the induction of cartilage.

Although the conserved signaling pathways that act during tail regeneration remain mainly uncharacterized it has been reported that many blastema cells are positive for phosphorylated SMAD2, a mediator of the TGFB/activin pathway, and the epithelial-mesenchymal transition markers Snail1 and Snail2.

In summary, many questions need to be answered concerning lizard tail regeneration especially on the source (stem/progenitor cells/dedifferentiation/transdifferentiation) and properties of the blastema cells (proliferative or non-proliferative).