Two of the interesting issues on the field of regeneration are why closely related species show very distinct regenerative capacities and why some species can regenerate certain organs or structures only during specific developmental stages. Therefore, detailed comparative analyses are fundamental to answer those questions which could help to enhance the poor regenerative power showed by many species. Axolotls are a classical model for limb and tail regeneration; however, lens regeneration was supposed not to happen in these animals. This was in contrast to other amphibians such as newts and frogs. Newts can regenerate their lens no matter their age and as many times as needed; frogs can also regenerate the lens but only at pre-metamorphic stages. Another difference among newts and frogs is that whereas in newts the lens regenerates from the dorsal iris epithelium by transdifferentation, in frogs it regenerates from the cornea (also through transdifferentiation). Now a paper from the laboratory of Panagiotis Tsonis has described that axolotls can in fact regenerate the lens but only during a specific developmental period (http://www.ncbi.nlm.nih.gov/pubmed/23244204). At stage 44 and during about two weeks, lens regeneration is permissive. Moreover, the new lens can regenerate either from the dorsal or ventral iris epithelium. Thus, we have an example of three amphibian species that show different levels of plasticity and strategies for lens regeneration. A possible next step could be then to compare the permissive and non-permissive stages for axolotl lens regeneration at gene expression and cellular levels, for instance, to determine why regeneration can take place at that particular time.
This comparative approach is also stimulated in the commentary by Ashley Seifert and S Randal Voss on the paper by P. Tsonis (http://www.ncbi.nlm.nih.gov/pubmed/23336699) and that highlights the known relationship between loss of regenerative capabilities and aging. An extreme and surprising example of that is the fact that mice up to about one week old are capable of regenerating their heart, but thereafter regeneration capacity is completely lost. But aging is not the only factor to consider when addressing the loss of regenerative capabilities shown in nature. As pointed out by Seifert and Voss, evolution, life history, physiology and ontogeny are important factors to take in account. Finally, it would become also important to search for novel models of regeneration in order to analyze and compare different mechanisms and strategies for regeneration. In this sense the finding that the African spiny mice can regenerate the skin (http://www.ncbi.nlm.nih.gov/pubmed/23018966) means that some mammals retain higher regenerative capabilities that thought.