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. Deutsche Forschungsgemeinschaft – Center for Regenerative Therapies Dresden, Germany
  3. Max Planck Institute of Molecular Cell Biology and Genetics, Germany
  4. Center for Advancing Electronics Dresden, Germany
  5. National Scientific and Technical Research Council, University of La Plata, Argentina
4 figures

Figures

Figure 1 with 1 supplement
Spinal cord outgrowth time-course during regeneration.

(A) Representative images of a regenerating spinal cord after tail amputation (individual time-lapse images are in Figure 1—figure supplement 1). The white dashed line marks the amputation plane. …

https://doi.org/10.7554/eLife.20357.002
Figure 1—figure supplement 1
Images used for spinal cord outgrowth measurements in Figure 1B.

Each row shows images from an axolotl; each column shows animals from one time point analyzed. Vertical and horizontal green lines mark the amputation plane and the spinal cord outgrowth, …

https://doi.org/10.7554/eLife.20357.003
Figure 2 with 5 supplements
Cellular mechanisms underlying spinal cord outgrowth.

(A) Sketch of measurements taken to estimate the density and total number of neural stem cells (nuclei, black dots) in the axolotl spinal cord. The density of SOX2+ cells, ρ, is the ratio of the …

https://doi.org/10.7554/eLife.20357.004
Figure 2—figure supplement 1
Number of SOX2+ cells per cross section along the AP axis for all 15 animals.

Each row shows data from three animals at a given time point. Data from animals 0D_1 and 4D_3 are shown as representative data in Figure 2B and B’, respectively.

https://doi.org/10.7554/eLife.20357.005
Figure 2—figure supplement 2
Simulation of the spatial model of cell counts to analyze the spatiotemporal pattern of cell proliferation.

(A) Simulations of a spatially homogeneous zone of proliferation for three animals. Population mean number of stem cells per cross section, NSpop = 7, inter-animal standard deviation for number of …

https://doi.org/10.7554/eLife.20357.006
Figure 2—figure supplement 3
Number of SOX2+/PCNA+ cells per cross section (upper panel) and mitotic cells per section (lower panel) along the AP axis for all 15 animals.

Data from animals 0D_1 and 4D_3 are shown in Figure 2D and D’, respectively. Each row shows data from three animals at a given time point.

https://doi.org/10.7554/eLife.20357.007
Figure 2—figure supplement 4
Posterior marginal distributions for the parameters of the spatial model of cell counts to analyze the spatiotemporal pattern of proliferation.

Each row shows a different model parameter. Each column shows a different time point. Three animals per time point were used in the analysis. Vertical dashed lines show the limits of the 95% …

https://doi.org/10.7554/eLife.20357.008
Figure 2—figure supplement 5
Cell cycle length time-course calculated from the proliferation rate time-course shown in Figure 2G.
https://doi.org/10.7554/eLife.20357.009
Figure 3 with 2 supplements
Mechanistic model of spinal cord outgrowth.

(A) Sketch of cellular mechanisms included in the model: cell proliferation, quiescent cell activation, and cell influx into the 800 μm high-proliferation zone. (B) Growth fraction time-course of …

https://doi.org/10.7554/eLife.20357.010
Figure 3—figure supplement 1
Prediction of the growth fraction in the high-proliferation zone for four model scenarios with selected mechanisms switched off (green shaded areas).

Black dots show the same experimental data as in Figure 3B. Scenarios in panels A-D correspond to the scenarios in Figure 3D–G, respectively. Switching off the acceleration of the cell cycle length …

https://doi.org/10.7554/eLife.20357.011
Figure 3—figure supplement 2
Comparison of the spinal cord outgrowth prediction by our model with the measured outgrowth reported by Fei et al. (2014).

(A) Outgrowth prediction of the full model (green, same as in Figure 3C) and rescaled outgrowth in the control condition from Fei et al., 2014 (black dot, n = 12 axolotls). (B) Outgrowth prediction …

https://doi.org/10.7554/eLife.20357.012
Conceptual model of spinal cord growth during regeneration.

Only one row of stem cells is shown as circles and three cell clones are marked with different patterns (striped, black and dotted). In the uninjured spinal cord (Day 0), cells divide at a slow, …

https://doi.org/10.7554/eLife.20357.013

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