1. Cell Biology
  2. Stem Cells and Regenerative Medicine

Planar cell polarity-mediated induction of neural stem cell expansion during axolotl spinal cord regeneration

  1. Aida Rodrigo Albors
  2. Akira Tazaki
  3. Fabian Rost
  4. Sergej Nowoshilow
  5. Osvaldo Chara
  6. Elly M Tanaka  Is a corresponding author
  1. Deutsche Forschungsgemeinschaft - Center for Regenerative Therapies Dresden, Germany
  2. Technische Universität Dresden, Germany
https://doi.org/10.7554/eLife.10230
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  1. Aida Rodrigo Albors
  2. Akira Tazaki
  3. Fabian Rost
  4. Sergej Nowoshilow
  5. Osvaldo Chara
  6. Elly M Tanaka
(2015)
Planar cell polarity-mediated induction of neural stem cell expansion during axolotl spinal cord regeneration
eLife 4:e10230.
https://doi.org/10.7554/eLife.10230
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Abstract

Axolotls are uniquely able to mobilize neural stem cells to regenerate all missing regions of the spinal cord. How a neural stem cell under homeostasis converts after injury to a highly regenerative cell remains unknown. Here we show that during regeneration, axolotl neural stem cells repress neurogenic genes and reactivate a transcriptional program similar to embryonic neuroepithelial cells. This dedifferentiation includes the acquisition of rapid cell cycles, the switch from neurogenic to proliferative divisions, and the re-expression of planar cell polarity (PCP) pathway components. We show that PCP induction is essential to reorient mitotic spindles along the anterior-posterior axis of elongation, and orthogonal to the cell apical-basal axis. Disruption of this property results in premature neurogenesis and halts regeneration. Our findings reveal a key role for PCP in coordinating the morphogenesis of spinal cord outgrowth with the switch from a homeostatic to a regenerative stem cell that restores missing tissue.

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Author details

  1. Aida Rodrigo Albors

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

  2. Akira Tazaki

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

  3. 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.

  4. Sergej Nowoshilow

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

  5. Osvaldo Chara

    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.

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 (Landesdirektion, Sachsen).

Copyright

© 2015, Rodrigo Albors 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. Aida Rodrigo Albors
  2. Akira Tazaki
  3. Fabian Rost
  4. Sergej Nowoshilow
  5. Osvaldo Chara
  6. Elly M Tanaka
(2015)
Planar cell polarity-mediated induction of neural stem cell expansion during axolotl spinal cord regeneration
eLife 4:e10230.
https://doi.org/10.7554/eLife.10230

Share this article

https://doi.org/10.7554/eLife.10230

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Further reading

    1. Computational and Systems Biology
    2. Developmental Biology

    Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration

    Emanuel Cura Costa, Leo Otsuki ... Osvaldo Chara
    Research Advance Updated

    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 modeling, 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 ~830 μm of the injury. We adapted Fluorescent Ubiquitination-based Cell Cycle Indicator (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.

    1. Computational and Systems Biology
    2. Stem Cells and Regenerative Medicine

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

    Fabian Rost, Aida Rodrigo Albors ... Osvaldo Chara
    Research Advance Updated

    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.

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