The Influence of the Nerve in Regeneration of the Amphibian Extremity

R EGENERATION is the replacement of lost parts by growth of new ones. It is observed widely among animals and plants and consists of the insensible, continuous replacement of cells, the renewal of damaged tissues, and the reproduction of organs, organ systems, and in some animals even entire regions of the body. The capacity to regenerate is highly limited in some forms and very extensive in others, and varies with age, being most extensive in the early embryo, which shows remarkable powers to renew damaged parts by the rearrangement and reorganization of available materials and by regrowth. The process of regeneration has recieved considerable attention from students of growth and development, since it emphasizes that regulated developmental capacities do not terminate with embryonic development but continue into the adult, albeit in a modified and restricted manner. In the experimental study of regeneration a number of forms have been favored because they show particularly well the ability to regenerate one or another part of the body or appendages. Coelenterates, fiatworms, earthworms, starfish, and crustaceans are the important invertebrate ones; and the urodele amphibians (salamanders and newts), the frog tadpole, the lizard, and some of the fishes are the vertebrate representatives. The regeneration process bears many resemblances to embryonic development and yet shows remarkable differences from it. Both the similarities and the differences have been the subject of considerable research. A striking similarity of regeneration to embryonic development is the accumulation in the region of injury of cells which have the disposition and appearance of the mesenchymal cells of the embryo, concentrations of which give rise to various organs. Moreover, the rapid growth of this cellular mass and its later structural and functional differentiation resemble closely embryonic formations in general appearance, arrangement, and developmental sequence. Yet regeneration cannot be equated with embryonic development, for the reason that the tissues which give rise to the new growth have a biological history and environment different from that of the embryo. The regenerate arises directly from and develops in intimate relation with adult structures, and there is no barrier between the new formation and the old tissues. The histology of the regenerate emphasizes the continuity and interrelation between adult and regenerating tissue, the former passing gradually into the latter with no absolute line of demarcation between the two. This intimacy of morphological relation between the regenerate and the adult tissue has demanded that study of the process of regeneration be made against the background of the anatomy and physiology of adult tissues. These relations with adult structures distinguish regeneration from embryonic development; they are various and, perhaps, more striking than the resemblances. The regenerate throughout its development is nourished by the adult blood stream, and there is no apparent obstacle to free exchange between the two, unless it be endothelial in nature. Thus the new growth is perfused continuously with substances of adult origin and importance. Adult epidermis adjacent to the wound area moves actively over the wound surface and forms the epithelial covering of the regenerate. The epidermis of the regenerate is thus continuous with the adult epidermis, although it is undoubtedly modified as it moves over the amputation surface, and therefore differs morphologically and physiologically from the adult epidermis (Godlewski, 1927; Orechowitsch and Bromley, 1934; Rose, 1948b; Singer, 1949; and others).