Multi-species atlas resolves an axolotl limb development and regeneration paradox

Jixing Zhong, Rita Aires, Georgios Tsissios, Evangelia Skoufa, Kerstin Brandt, Tatiana Sandoval-Guzmán () and Can Aztekin ()
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Jixing Zhong: Swiss Federal Institute of Technology Lausanne, EPFL
Rita Aires: University Hospital Carl Gustav Carus, Technische Universität Dresden
Georgios Tsissios: Swiss Federal Institute of Technology Lausanne, EPFL
Evangelia Skoufa: Swiss Federal Institute of Technology Lausanne, EPFL
Kerstin Brandt: University Hospital Carl Gustav Carus, Technische Universität Dresden
Tatiana Sandoval-Guzmán: University Hospital Carl Gustav Carus, Technische Universität Dresden
Can Aztekin: Swiss Federal Institute of Technology Lausanne, EPFL

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract Humans and other tetrapods are considered to require apical-ectodermal-ridge (AER) cells for limb development, and AER-like cells are suggested to be re-formed to initiate limb regeneration. Paradoxically, the presence of AER in the axolotl, a primary model organism for regeneration, remains controversial. Here, by leveraging a single-cell transcriptomics-based multi-species atlas, composed of axolotl, human, mouse, chicken, and frog cells, we first establish that axolotls contain cells with AER characteristics. Further analyses and spatial transcriptomics reveal that axolotl limbs do not fully re-form AER cells during regeneration. Moreover, the axolotl mesoderm displays part of the AER machinery, revealing a program for limb (re)growth. These results clarify the debate about the axolotl AER and the extent to which the limb developmental program is recapitulated during regeneration.

Date: 2023
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DOI: 10.1038/s41467-023-41944-w

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