Abstract
Absence of a specialised wound epidermis is hypothesised to block limb regeneration in higher vertebrates. To elucidate the cellular and molecular determinants of this tissue, we performed single-cell transcriptomics in regeneration-competent, -restricted, and -incompetent Xenopus tadpoles. We identified apical-ectodermal-ridge (AER) cells as the specialised wound epidermis, and found that their abundance on the amputation plane correlates with regeneration potential and injury-induced mesenchymal plasticity. By using ex vivo regenerating limb cultures, we demonstrate that extrinsic cues produced during limb development block AER cell formation. We identify Noggin, a morphogen expressed in cartilage/bone progenitor cells, as one of the key inhibitors of AER cell formation in regeneration-incompetent tadpoles. Extrinsic inhibitory cues can be overridden by Fgf10, which operates upstream of Noggin and blocks chondrogenesis. Together, these results indicate that manipulation of the extracellular environment and/or chondrogenesis may provide a strategy to restore regeneration potential in higher vertebrates.
One Sentence Summary Extrinsic cues associated with chondrogenic progression inhibit AER cell formation and restrict limb regeneration potential.
Competing Interest Statement
The authors have declared no competing interest.