Accelerated cell divisions drive the outgrowth of the regenerating spinal cord in axolotls

  1. Fabian Rost
  2. Aida Rodrigo Albors
  3. Vladimir Mazurov
  4. Lutz Brusch
  5. Andreas Deutsch
  6. Elly M Tanaka  Is a corresponding author
  7. Osvaldo Chara  Is a corresponding author
  1. Technische Universität Dresden, Germany
  2. University of Dundee, United Kingdom
  3. Deutsche Forschungsgemeinschaft - Center for Regenerative Therapies Dresden, Germany

Abstract

Axolotls are unique in their ability to regenerate the spinal cord. However, the mechanisms that underlie this phenomenon remain poorly understood. Previously, we showed that regenerating stem cells in the axolotl spinal cord revert to a molecular state resembling embryonic neuroepithelial cells and functionally acquire rapid proliferative divisions (Rodrigo Albors et al., 2015). Here, we refine the analysis of cell proliferation in space and time and identify a high-proliferation zone in the regenerating spinal cord that shifts posteriorly over time. By tracking sparsely-labeled cells, we also quantify cell influx into the regenerate. Taking a mathematical modeling approach, we integrate these quantitative datasets of cell proliferation, neural stem cell activation and cell influx, to predict regenerative tissue outgrowth. Our model shows that while cell influx and neural stem cell activation play a minor role, the acceleration of the cell cycle is the major driver of regenerative spinal cord outgrowth in axolotls.

Article and author information

Author details

  1. Fabian Rost

    Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6466-2589
  2. Aida Rodrigo Albors

    Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9573-2639
  3. Vladimir Mazurov

    Deutsche Forschungsgemeinschaft - Center for Regenerative Therapies Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Lutz Brusch

    Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Andreas Deutsch

    Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Elly M Tanaka

    Deutsche Forschungsgemeinschaft - Center for Regenerative Therapies Dresden, Dresden, Germany
    For correspondence
    elly.tanaka@crt-dresden.de
    Competing interests
    The authors declare that no competing interests exist.
  7. Osvaldo Chara

    Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany
    For correspondence
    osvaldo.chara@tu-dresden.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0868-2507

Funding

Human Frontier Science Program (RGP0016/2010)

  • Elly M Tanaka

Deutsche Forschungsgemeinschaft (DFG-274/2-3/SFB655)

  • Elly M Tanaka

Agencia Nacional de Promoción Científica y Tecnológica (PICT-2014-3469)

  • Osvaldo Chara

Bundesministerium für Bildung und Forschung (0316169A)

  • Lutz Brusch

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The axolotl animal work was performed under permission granted in animal license number DD24-9168.11-1/2012-13 conferred by the Animal Welfare Commission of the State of Saxony, Germany (Landesdirektion, Sachsen).

Copyright

© 2016, Rost et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Fabian Rost
  2. Aida Rodrigo Albors
  3. Vladimir Mazurov
  4. Lutz Brusch
  5. Andreas Deutsch
  6. Elly M Tanaka
  7. Osvaldo Chara
(2016)
Accelerated cell divisions drive the outgrowth of the regenerating spinal cord in axolotls
eLife 5:e20357.
https://doi.org/10.7554/eLife.20357

Share this article

https://doi.org/10.7554/eLife.20357

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