The effects of local application of retinoic acid on limb development and regeneration in tadpoles of Xenopus

Vitamin A can have different effects on developing and regenerating limbs depending on the mode of administration. Previous work has demonstrated the differential effect of retinol palmitate on limb development and regeneration in Xenopus laevis. The purpose of the present investigation was to determine the effects of vitamin A on limb development and regeneration in Xenopus when administered by a local implantation method. Xenopus tadpoles had both hindlimbs implanted with either a block of silastin carrying retinoic acid or an anion exchange resin bead carrying retinoic acid and then the right hindlimb was amputated and the effect of the retinoic acid on limb development and regeneration was studied. The results showed that in developing hindlimbs the effects of silastin implants carrying retinoic acid was to cause skeletal reductions or deletions similar to those induced by immersion of the tadpole in retinol palmitate. On the other hand, in regenerating hindlimbs, the silastin implants caused a range of skeletal reductions and deletions as well as occasional accessory structures but notably induced no proximodistal (PD) duplications, unlike the effect of immersion in retinol palmitate where PD duplications were a common response. Implantation of anion exchange resin beads carrying retinoic acid had no significant effect on either development or regeneration beyond stage 50, presumably because the dose of the retinoic acid was so low. Thus the results suggest that the mode of administration of vitamin A has a very significant influence on its effects. The significance of this observation for vitamin A experiments on limbs is discussed.