An international team of scientists led by the labs of Elly Tanaka at the Research Institute of Molecular Pathology and Barbara Treutlein at ETH Zurich zoomed in on the regeneration abilities of axolotls. Their study, published in Developmental Cell gives away the cellular and molecular bases that lead to the incomplete limb regeneration in African clawed frogs (Xenopus laevis). The researchers compared the regeneration process in frogs and axolotls (Ambystoma mexicanum) using genetic fate-mapping and state-of-the-art single cell RNA-seq technologies. Their findigs show that frog cells have cell intrinsic barriers to become fully de-differentiated to a limb bud-like progenitor state, which correlates with the regeneration outcome. This work opens the door to further disentangling the (epi)genetic networks underlying the secret of limb regeneration.