When thinking about regeneration in nature one cannot be anything else than amazed when seeing how, for example, axolotls regenerate their limbs, zebrafish make new hearts or Hydra and planarians regenerate a whole animal from a tiny piece of their bodies. Regeneration is widely distributed throughout the phylogenetic tree although it is also evident that the capacity to regenerate can vary a lot not only among different animal phyla but also among closed species belonging to the same phylum, class or family. Regeneration can take place at different biological levels: whole body, structure (limb, fin, tail, tentacle,…), organ (heart, lens,…), tissue and cell; different species may show then different regenerative responses along those different levels. Of course, one of the first questions that comes to most people is why some animals can regenerate and others not? Here, we need to take in account, among others, the relation between regeneration and asexual reproduction, the evolutionary history, ecological factors and aging and developmental stage. It becomes important then to carry out comparative studies between very close phylogenetically related species that, on the other side, display very different regenerative capacities. Is regeneration an ancestral trait of animals that has been lost in many lineages, or has regeneration appeared independently several times throughout evolution?
A second set of important questions to address refer to how structure, form and polarity are reestablished during regeneration. To answer those questions we can focus, among others, on what are the signals that initiate the regenerative response? How are these signals linked to wound healing? Thus, for example, manipulating the way that wound heals in injured mammalian skin it is possible to trigger a scarless regenerative response, that normally does not take place. Then, we need to investigate how axial polarity is reestablished and what the signals and pathways that control growth and patterning of the new tissues, organs, structures or body parts. An important aspect of regeneration is that in most cases animals regenerate just what they have lost and they do it in a precise way so the regenerated new structure is identical to the original.
Finally, another basic question relates to the origin of the regenerating cells. It is obvious that in order to rebuild any missing part we need a source of new cells. Different models of regeneration use different sources of new cells, ranging from hyperplasia (proliferation of differentiated cells), direct transdifferentiation, dedifferentiation towards a more or less uni-, multi- or pluripotent state and subsequent redifferentiation, to, finally, the use of adult stem cells. Regardless of the particular scenario, understanding the molecular regulation of all those cellular sources together with a detailed characterization on how the different cell lineages are restored will have an impact not only on animal regeneration but also on regenerative medicine.