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Cells keep a memory of their tissue origin during axolotl limb regeneration

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  • Martin Kragl

    (Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108,
    Center for Regenerative Therapies, University of Technology Dresden, Tatzberg 47/49, 01307 Dresden, Germany
    Present address: Institute of Metabolic Physiology, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.)

  • Dunja Knapp

    (Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108,
    Center for Regenerative Therapies, University of Technology Dresden, Tatzberg 47/49, 01307 Dresden, Germany)

  • Eugen Nacu

    (Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108,
    Center for Regenerative Therapies, University of Technology Dresden, Tatzberg 47/49, 01307 Dresden, Germany)

  • Shahryar Khattak

    (Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108,
    Center for Regenerative Therapies, University of Technology Dresden, Tatzberg 47/49, 01307 Dresden, Germany)

  • Malcolm Maden

    (The Regeneration Project, McKnight Brian Institute, University of Florida, Rm 326 Bartram Hall, Gainesville, Florida 32611, USA)

  • Hans Henning Epperlein

    (Institute of Anatomy, Medical Faculty, University of Technology Dresden, Fetscherstrasse 74,)

  • Elly M. Tanaka

    (Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108,
    Center for Regenerative Therapies, University of Technology Dresden, Tatzberg 47/49, 01307 Dresden, Germany)

Abstract

During limb regeneration adult tissue is converted into a zone of undifferentiated progenitors called the blastema that reforms the diverse tissues of the limb. Previous experiments have led to wide acceptance that limb tissues dedifferentiate to form pluripotent cells. Here we have reexamined this question using an integrated GFP transgene to track the major limb tissues during limb regeneration in the salamander Ambystoma mexicanum (the axolotl). Surprisingly, we find that each tissue produces progenitor cells with restricted potential. Therefore, the blastema is a heterogeneous collection of restricted progenitor cells. On the basis of these findings, we further demonstrate that positional identity is a cell-type-specific property of blastema cells, in which cartilage-derived blastema cells harbour positional identity but Schwann-derived cells do not. Our results show that the complex phenomenon of limb regeneration can be achieved without complete dedifferentiation to a pluripotent state, a conclusion with important implications for regenerative medicine.

Suggested Citation

  • Martin Kragl & Dunja Knapp & Eugen Nacu & Shahryar Khattak & Malcolm Maden & Hans Henning Epperlein & Elly M. Tanaka, 2009. "Cells keep a memory of their tissue origin during axolotl limb regeneration," Nature, Nature, vol. 460(7251), pages 60-65, July.
  • Handle: RePEc:nat:nature:v:460:y:2009:i:7251:d:10.1038_nature08152
    DOI: 10.1038/nature08152
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    Cited by:

    1. Béryl Laplace-Builhé & Audrey Barthelaix & Said Assou & Candice Bohaud & Marine Pratlong & Dany Severac & Gautier Tejedor & Patricia Luz-Crawford & Mai Nguyen-Chi & Marc Mathieu & Christian Jorgensen , 2021. "NRG1/ErbB signalling controls the dialogue between macrophages and neural crest-derived cells during zebrafish fin regeneration," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Thomas P. Lozito & Ricardo Londono & Aaron X. Sun & Megan L. Hudnall, 2021. "Introducing dorsoventral patterning in adult regenerating lizard tails with gene-edited embryonic neural stem cells," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Jixing Zhong & Rita Aires & Georgios Tsissios & Evangelia Skoufa & Kerstin Brandt & Tatiana Sandoval-Guzmán & Can Aztekin, 2023. "Multi-species atlas resolves an axolotl limb development and regeneration paradox," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Daniel H Rapoport & Tim Becker & Amir Madany Mamlouk & Simone Schicktanz & Charli Kruse, 2011. "A Novel Validation Algorithm Allows for Automated Cell Tracking and the Extraction of Biologically Meaningful Parameters," PLOS ONE, Public Library of Science, vol. 6(11), pages 1-16, November.

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