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.
Institut(e)Institute of Pancreatic Islet Research (IPI)
FörderungenVon Humboldt Foundation Research fellowship SNSF Foundation Gabriella Giorgi-Cavaglieri, Branco Weiss Fellowship A. Petzold and the CM M. Ros, D. Suter, G. La Manno, and M. Gurel for their critical reading of the manuscript M. Gurel and M. Brbic for discussions on factorization and module identification We thank Aztekin and Sandoval-Guzman Labs for the discussions