1. Computational and Systems Biology
  2. Developmental Biology
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Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration

  1. Emanuel Cura Costa
  2. Leo Otsuki
  3. Aida Rodrigo Albors
  4. Elly M Tanaka
  5. Osvaldo Chara  Is a corresponding author
  1. National Scientific and Technical Research Council (CONICET) and University of La Plata (UNLP), Argentina
  2. Vienna Biocenter (VBC), Austria
  3. University of Dundee, United Kingdom
  4. Technische Universität Dresden, Germany
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Cite this article as: eLife 2021;10:e55665 doi: 10.7554/eLife.55665

Abstract

Axolotls are uniquely able to resolve spinal cord injuries, but little is known about the mechanisms underlying spinal cord regeneration. We previously found that tail amputation leads to reactivation of a developmental-like program in spinal cord ependymal cells (Rodrigo Albors et al., 2015), characterized by a high-proliferation zone emerging 4 days post-amputation (Rost et al., 2016). What underlies this spatiotemporal pattern of cell proliferation, however, remained unknown. Here, we use modelling, tightly linked to experimental data, to demonstrate that this regenerative response is consistent with a signal that recruits ependymal cells during ~85 hours after amputation within ~830mm of the injury. We adapted FUCCI technology to axolotls (AxFUCCI) to visualize cell cycles in vivo. AxFUCCI axolotls confirmed the predicted appearance time and size of the injury-induced recruitment zone and revealed cell cycle synchrony between ependymal cells. Our modeling and imaging move us closer to understanding bona fide spinal cord regeneration.

Data availability

Jupyter Notebook (http://jupyter.org/) containing the source code for all computations performed and referred to as Cura Costa et al., 2021 in this study can be found at https://doi.org/10.5281/zenodo.4557840

Article and author information

Author details

  1. Emanuel Cura Costa

    Systems Biology Group (SysBio), Institute of Physics of Liquids and Biological Systems (IFLySIB), National Scientific and Technical Research Council (CONICET) and University of La Plata (UNLP), La Plata, Argentina
    Competing interests
    The authors declare that no competing interests exist.
  2. Leo Otsuki

    The Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6107-2508
  3. 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
  4. Elly M Tanaka

    The Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4240-2158
  5. 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

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

  • Osvaldo Chara

Agencia Nacional de Promoción Científica y Tecnológica (PICT 2017-2307)

  • Osvaldo Chara

Agencia Nacional de Promoción Científica y Tecnológica (PICT-2019-2019-03828)

  • Osvaldo Chara

Consejo Nacional de Investigaciones Científicas y Técnicas (Doctoral Student Fellowship)

  • Emanuel Cura Costa

ERC Advanced Grant (742046)

  • Elly M Tanaka

Human Frontier Science Program (fellowship LT000785/2019-L.)

  • Leo Otsuki

European Union's Horizon 2020 research and innovation programme (Marie Skłodowska-Curie grant agreement No 753812)

  • Aida Rodrigo Albors

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 licenses necessary for work with genetically modified organisms (GMOs) and for experiments specifically involving axolotls (Ambystoma mexicanum) were obtained from the relevant authorities and have been implemented at the IMP in accordance with applicable international, EU and national (Austrian) guidelines.The license for work with GMOs at safety levels 1 and 2 was approved by the GMO office of the Austrian authorities and was issued on 16/03/2017 with no end date (BMGF‐76110/0017‐ II/B/16c/2017).The axolotl research license numbers are GZ: 51072/2019/16 (valid 09/05/2019 - 28/02/2024) and GZ: MA58/665226/2019/21 (valid 24.02.2020 - 30.09.2024). These are approved by the City of Vienna, MA58.There is a dedicated veterinarian for the animal facility, as well as an animal welfare consultant. Animal facility inspections are performed yearly by the City of Vienna, MA58 and the animal licenses and animal husbandry conditions are updated in dialogue with animal welfare authorities.Axolotls (Ambystoma mexicanum) were raised in individual aquaria. Axolotl breedings were performed by the IMP animal facility. All experiments were performed in accordance with locally applicable ethics committee guidelines and within a framework agreed with the Magistrate of Vienna (Austria). Axolotls were anaesthetized with benzocaine (Sigma) diluted in tap water prior to amputation and/or imaging, to minimize suffering.

Reviewing Editor

  1. Alejandro Sánchez Alvarado, Stowers Institute for Medical Research, United States

Publication history

  1. Received: February 10, 2020
  2. Accepted: May 13, 2021
  3. Accepted Manuscript published: May 14, 2021 (version 1)

Copyright

© 2021, Cura Costa 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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