Tissue composition shapes differential skeletal integration strategies during axolotl limb regeneration
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.
Authors
- Rita Aires (ORCID: https://orcid.org/0000-0002-3537-0453)
- Sean D. Keeley (ORCID: https://orcid.org/0000-0002-2429-3253)
- Ulrike Anne Friedrich (ORCID: https://orcid.org/0000-0001-7295-4549)
- Andreas Dahl (ORCID: https://orcid.org/0000-0002-2668-8371)
- Can Aztekin (ORCID: https://orcid.org/0000-0002-6544-9752)
- Yağız Savcı (ORCID: https://orcid.org/0000-0003-1198-9099)
- Tatiana Sandoval‐Guzmán (ORCID: https://orcid.org/0000-0003-1802-5145)
- Kerstin Brandt
- Mário Carreira (ORCID: https://orcid.org/0009-0005-4772-4449)
- Doğa Berşan Güneş (ORCID: https://orcid.org/0009-0005-1949-8165)
- Pedro Capucho (ORCID: https://orcid.org/0009-0006-7416-4923)
Institutions
- Max Planck Society (DE)
- Universidade do Porto (PT)
- Friedrich Miescher Laboratory (DE)
- Center for Systems Biology Dresden (DE)
- Deutsches Diabetes-Zentrum e.V. (DE)
- German Center for Diabetes Research (DE)
- University Hospital Carl Gustav Carus (DE)
- Paul Langerhans Institute Dresden (DE)
- Instituto de Ciências Biomédicas Albel Salazar (PT)
- Center for Regenerative Therapies Dresden (DE)
- DRESDEN-concept Genome Center (DE)
- Center for Molecular and Cellular Bioengineering (DE)
- Heinrich Heine University Düsseldorf (DE)
- Istanbul Technical University (TR)
- Technische Universität Dresden (DE)
- Universidade Nova de Lisboa (PT)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-10-15
- DOI
- https://doi.org/10.1038/s41467-026-78607-5
- Primary Topic
- Planarian Biology and Electrostimulation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Alexander von Humboldt-Stiftung
- Deutsche Forschungsgemeinschaft