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The anuran amphibian Xenopus laevis can regenerate its limbs for a limited time during the larval stage, while limbs are still developing. Using this regeneration model, we evaluated the proximo-distal blastema cell identity when endogenous retinoids were increased by CYP26 inhibition or when RAR-specific agonists altered RA signaling. Simultaneous proximo-distal and antero-posterior limb duplications were generated, and the RAR-specific agonist can modify blastema identity after amputation, because chemical activation of RARβ produced bilateral hindlimb duplications that resulted in a drastic duplication phenotype of regenerating limbs.

Chemical activation of RARβ induces post-embryonically bilateral limb duplication during Xenopus limb regeneration