THE LOSS AND RESTORATION OF REGENERATIVE CAPACITY IN THE LIMBS OF TAILLESS AMPHIBIA 1

(I) When the hindlimbs of Rana temporaria are amputated in the proximal part of the shank during stage I of metamorphosis they regenerate, but they lose their regenerative capacity at stage II. The regenerative capacity is retained longer in the distal than in the proximal parts of the limbs, which is due to the process of histological differentiation taking place in a proximal‐distal direction. (a) When the amputation is made during stage I the mesodermal tissue of the limbs dedifferentiates, regenerative blastemata are formed and the limbs regenerate. When the amputation is made during a later stage the mesodermal tissue does not dedifferentiate, blastemata are not formed and the limbs do not regenerate. (3) By a traumatization or a transplantation it is possible to excite complete regeneration at those stages in which the opposite (control) limbs of the same animals do not regenerate. (4) The restoration of the regenerative capacity of the limbs of tadpoles is brought about by the dedifferentiation of the mesodermal tissue in the distal part of the stump and not by an acceleration of the process of cell proliferation. (5) The regenerative capacity of tadpoles' limbs may be extended by means of repeated regeneration to a late stage of metamorphosis, or. indeed, up to the completion of this process. The re‐newal of the regenerative capacity is dependent on the retention of the mesodermal tissue of the limbs at a level of histological differentiation which permits of de‐differentiation. (6) The regeneration of the limbs of Anura and Urodela occurs in two phases: during the first phase the blastemata are formed almost entirely without mitosis, by the direct liberation of cells from the dedifferentiating mesodermal tissue; during the second phase the blastemata are formed mainly through intensified cell proliferation. (7) Tadpoles' limbs regenerate much more quickly, their mesodermal tissue dedifferentiates much more profoundly, and the mitotic coefficient is much lower than in the case of Urodela (axolotls). The difficulty of dedifferentiation, therefore must have a stronger inhibiting influence on the regeneration of tadpoles' limbs than on those of axolotls. (8) During the process of metamorphosis the internal humoral medium of the animal undergoes changes due to which there is an acceleration of the histological differentiation of the limbs and a suppression of the possibility of dedifferentiation and the formation of blastemata. (9) During metamorphosis, together with the loss of regenerative capacity, changes take place in the properties of the epithelium and of the mesodermal tissue of tadpoles' limbs. Changes in the mesoderm have a stronger and more profound influence on the regenerative capacity than changes in the epithelium. (10) Changes in the nervous system have no important effect on the regenerative capacity of tadpoles' limbs, (n) The loss of regenerative capacity in tadpoles' limbs is connected primarily with histological differentiation. This may to a certain extent occur independently of the changes that take place in the internal humoral medium, but in a typical case it is accelerated by these changes. (12) The main factor causing a loss of regenerative capacity in tadpoles' limbs is the histological differentiation of the mesodermal tissue and its inability to dedifferentiate. (13) To restore the regenerative capacity of the limbs of Anura the formation of blastemata must be effected, for which it is primarily necessary to cause dedifferentiation in the mesodermal tissue of the stump.