Tissue composition shapes differential skeletal integration strategies during axolotl limb regeneration [Spatial Transcriptomics]

Osteoclast-mediated tissue resorption is essential for skeletal integration during regeneration. However, it is unknown if skeletal tissue composition impacts its resorption and, if so, how it is regulated.

Here, we show that osteoclast-mediated skeletal resorption is activated in amputations damaging the diaphysis, but not the epiphysis, of skeletal elements. We found that amputations in the calcified diaphysis trigger the sustained expression of RANKL and the chemokine Loc483, and that the latter is sufficient to induce osteoclast presence in non-resorbing amputations. Finally, our data suggests that the transcriptomic profile of the apical ectodermal cap is impacted by the tissues injured by the amputation.