Tissue composition shapes differential skeletal integration strategies during axolotl limb regeneration
Abstract
Limb regeneration requires rebuilding the missing structures and integrating them with stump tissues. 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 epithelial cap is impacted by the tissues injured by the amputation. Overall, our work reveals that tissue composition at the amputation plane shapes adaptations of the regenerative program, which ultimately contribute to the near-seamless tissue integration of the regenerating axolotl limb regardless of the amputation position.
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BibTeX
@article{aires2026tissue,
title = {{Tissue composition shapes differential skeletal integration strategies during axolotl limb regeneration}},
author = {Rita Aires and Sean D. Keeley and Kerstin Brandt and Mário Carreira and Doğa Berşan Güneş and Yağız Savcı and Pedro Capucho and Ulrike Anne Friedrich and Andreas Dahl and Can Aztekin and Tatiana Sandoval-Guzmán},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78607-5},
url = {https://www.nature.com/articles/s41467-026-78607-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Tissue composition shapes differential skeletal integration strategies during axolotl limb regeneration
AU - Rita Aires
AU - Sean D. Keeley
AU - Kerstin Brandt
AU - Mário Carreira
AU - Doğa Berşan Güneş
AU - Yağız Savcı
AU - Pedro Capucho
AU - Ulrike Anne Friedrich
AU - Andreas Dahl
AU - Can Aztekin
AU - Tatiana Sandoval-Guzmán
PY - 2026
DA - 2026/10/15
JO - Nature Communications
DO - 10.1038/s41467-026-78607-5
UR - https://www.nature.com/articles/s41467-026-78607-5
AB - Limb regeneration requires rebuilding the missing structures and integrating them with stump tissues. 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 epithelial cap is impacted by the tissues injured by the amputation. Overall, our work reveals that tissue composition at the amputation plane shapes adaptations of the regenerative program, which ultimately contribute to the near-seamless tissue integration of the regenerating axolotl limb regardless of the amputation position.
SN - 2041-1723
ER -