/. Embryo!, exp. Morph. Vol. 41, pp. 1-13, 1977 Primed in Great Britain <& Company of Biologists Limited 1977 The role of Schwann cells in paradoxical regeneration in the axolotl By M. MADEN 1 From the Department of Genetics, University of Birmingham SUMMARY The experiments described here examine further the conditions under which paradoxical regeneration occurs and provide support for the hypothesis that a proximal migration of Schwann cells is responsible for the phenomenon. When only the hand is shielded from irradi- tion and the limb is denervated, amputation through the forearm or upper arm sometimes results in regeneration. The effects of variation in the time interval between denervation and amputation, the level of amputation and the method and number of denervations on the incidence of regeneration were investigated. The presence or absence of viable Schwann cells at the amputation plane was deduced from the remyelination of nerves under conditions which do or do not permit paradoxical regeneration. The nerves of totally irradiated and denervated limbs remain unmyelinated following regrowth of axons and such limbs do not regenerate after amputation. When only the hand was shielded from irradiation before the limbs were denervated, the new axons became completely remyelinated and some of these limbs regenerated when amputated. It is suggested that under these conditions Schwann cells can migrate proximally and can then proliferate further to form a blastema, since they would be the only unirradiated tissue present at the amputation plane. INTRODUCTION When amputated through a region which has been irradiated with 2000R of X-rays, the limbs of young axolotls do not regenerate (Maden & Wallace, 1976). Limbs often do regenerate, however, if they have been denervated shortly after irradiation and well before amputation (Wallace, 1972). The subsequent regrowth of nerves from the shielded brachial plexus after denervation restored the regenerative ability of a proportion of arms when amputated through the irradiated forearm several weeks later. Regrowth of axons from an irradiated brachial plexus through a shielded region above the elbow into the irradiated forearm also permitted regeneration after amputation at the wrist. An even more striking demonstration ensued when only the hand and wrist were shielded before denervation; here, amputation in the mid-forearm four weeks later resulted in the regeneration of half of the specimens after a considerable delay. The contralateral arms, identical except that they had not been dener- vated, did not regenerate, confirming that paradoxical regeneration, as Wallace (1972) termed it, is dependent on the effects of denervation. 1 Authors address: Developmental Biology Group, School of Biological Sciences, Uni- versity of Sussex, Brighton, BN1 9QG, Sussex, U.K.