Dicer inactivation stimulates limb regeneration ability in Xenopus laevis

The ontogenetic decline of regeneration capacity in the anuran amphibian Xenopus makes it an excellent model for regeneration studies. However, the cause of the regeneration ability decline is not fully understood. MicroRNAs regulate animal development and have been indicated in various regeneration situations. However, little is known about the role of microRNAs during limb regeneration in Xenopus. This study investigates the effect of Dicer, an enzyme responsible for microRNA maturation, on limb development and regeneration in Xenopus. Dicer is expressed in the developing Xenopus limbs and is up-regulated after limb amputation during both regeneration-competent and regeneration-deficient stages of tadpole development. Inactivation of Dicer in early (NF stage 53) tadpole limb buds leads to shorter tibulare/fibulare formation but does not affect limb regeneration. However, in late-stage, regeneration-deficient tadpole limbs (NF stage 57), Dicer inactivation restores the regeneration blastema and stimulates limb regeneration. Thus, our results demonstrated that Xenopus limb regeneration can be stimulated by the inactivation of Dicer in nonregenerating tadpoles, indicating that microRNAs present in late-stage tadpole limbs may be involved in the ontogenetic decline of limb regeneration in Xenopus.