Nerve-independence of limb regeneration in larval Xenopus laevis is related to the presence of mitogenic factors in early limb tissues

Early limbs of larval Xenopus laevis can form a regeneration blastema in th e absence of nerves. The nerve-independence could be due to the synthesis o f neurotrophic-like factors by the limb bud cells. To test this hypothesis, two series of experiments were performed. Series A: the right hindlimbs of stage 57 larvae (acc. to Nieuwkoop and Faber. 1956. Normal table of Xenopu s laevis [Daudin]. Amsterdam: North-Holland Pub. Co.), which are nerve-depe ndent for regeneration, were amputated through the tarsalia. The regenerati ng limbs were submitted to: sham denervation; denervation; denervation and implantation of a fragment of an early limb, or a late limb, or a spinal co rd. Series B: froglets were subjected to amputation of both forelimbs. The cone blastemas were transplanted into denervated hindlimbs of stage 57 larv ae, together with a fragment of an early or a late limb. The results in ser ies A showed that the implantation of early limb tissue into the denervated blastema maintained cell proliferation at levels similar to those observed after the implantation of a spinal cord fragment or in sham denervated bla stemas. However, the implantation of late limb tissues were ineffective. Th e results of series B showed that the implantation of early limb tissue, bu t not of late limb tissue, prevented the inhibition of cell proliferation a nd the regression of denervated limb blastemas of juveniles. These results indicate that the nerve-independence is related to the synthesis of diffusi ble mitogenic neurotrophic-like factors in early limb tissues, and that ner ve-dependence is established when differentiated cells of late limb tissues stop producing these factors. J. Exp. Zool. 284:188-196, 1999. (C) 1999 Wi ley-Liss, Inc.