The Nerve Dependence of Amphibian Limb Regeneration

The regeneration of limbs in urodele amphibians is a context where the developing and regenerating peripheral nervous system interacts with the mechanisms of epimorphic regeneration. After amputation of a limb, there arise at the amputation plane the blastemal cells which are the progenitor cells of the regenerate. These cells divide rapidly and subsequently differentiate to give rise to the internal tissues (cartilage, muscle and connective tissue) of the regenerate. Division of the blastemal cells requires the presence of nerve axons at the amputation plane, at least during the initial stages of regeneration. This requirement can be circumvented by allowing a limb to develop in the absence of a nerve supply (the 'aneurogenic limb'), but the underlying mechanisms have been unclear. We have derived a monoclonal antibody called 22/18 that has provided new information about these issues. It is specific for blastemal cells versus normal tissue in the limb, specific for regeneration versus development, and specific for blastemal cells that arise after amputation in the presence of the nervous system versus its absence (in either development or the aneurogenic limb). The antibody reactivity appears to mark a cell transition involved in the imposition of nerve-dependent growth control.