Accelerated cell divisions drive the outgrowth of the regenerating spinal cord in axolotls
- Technische Universität Dresden, Germany
- University of Dundee, United Kingdom
- 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
Aida Rodrigo Albors
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.
Reviewing Editor
- Marianne Bronner, California Institute of Technology, United States
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).
Version history
- Received: August 8, 2016
- Accepted: November 14, 2016
- Accepted Manuscript published: November 25, 2016 (version 1)
- Version of Record published: December 23, 2016 (version 2)
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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Accelerated cell divisions drive the outgrowth of the regenerating spinal cord in axolotls
eLife 5:e20357.
https://doi.org/10.7554/eLife.20357
Further reading
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- Cell Biology
- Stem Cells and Regenerative Medicine
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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- Computational and Systems Biology
Transcriptomic profiling became a standard approach to quantify a cell state, which led to accumulation of huge amount of public gene expression datasets. However, both reuse of these datasets or analysis of newly generated ones requires significant technical expertise. Here we present Phantasus - a user-friendly web-application for interactive gene expression analysis which provides a streamlined access to more than 96000 public gene expression datasets, as well as allows analysis of user-uploaded datasets. Phantasus integrates an intuitive and highly interactive JavaScript-based heatmap interface with an ability to run sophisticated R-based analysis methods. Overall Phantasus allows users to go all the way from loading, normalizing and filtering data to doing differential gene expression and downstream analysis. Phantasus can be accessed on-line at https://alserglab.wustl.edu/phantasus or can be installed locally from Bioconductor (https://bioconductor.org/packages/phantasus). Phantasus source code is available at https://github.com/ctlab/phantasus under MIT license.
