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bioRxiv · 10.1101/2020.06.01.127654

Secreted inhibitors drive the loss of regeneration competence in Xenopus limbs

Aztekin, C.·Hiscock, T.·Gurdon, J.·Jullien, J.·Marioni, J.·Simons, B. D.
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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 SummaryExtrinsic cues associated with chondrogenic progression inhibit AER cell formation and restrict limb regeneration potential.

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Aztekin, C., Hiscock, T., Gurdon, J., Jullien, J., Marioni, J., Simons, B. D.. 2020-06-02. Secreted inhibitors drive the loss of regeneration competence in Xenopus limbs. https://doi.org/10.1101/2020.06.01.127654

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