Novel insights into the flexibility of cell and positional identity during urodele limb regeneration

The ability of diverse metazoans to regenerate whole-body structures was first described systematically by Spallanzani in 1768 and continues to fascinate biologists today. Given the current interest in stem cell biology and its therapeutic potential, examples of vertebrate regeneration garner strong interest. Among regeneration-competent vertebrates such as the fish, frog, and salamander, the salamander is particularly impressive because it can regenerate the entire limb and tail as well as various internal organs as an adult (Goss 1969). This spectacular natural phenomenon leads us to ask what cellular properties allow regeneration and what prevents this phenomenon in other vertebrates. From this perspective, it is imperative to know whether the stem cells in regenerating limbs harbor particularly special traits such as a higher plasticity in cell fate compared to tissue stem cells in other organisms. Flexibility in cell fate needs to be considered with respect not only to tissue identity, but also to patterning because limb amputation causes cells in a particular limb segment to form more distal limb elements. How positional identity is encoded in stem cells and how it is controlled to produce only the missing portion of the limb are also questions of fundamental importance.