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

eLife, 2016 · DOI: 10.7554/eLife.20357.001 · Published: November 25, 2016

Regenerative Medicine Genetics Bioinformatics

Simple Explanation

Axolotls can regenerate their spinal cords. This study looks at how this happens at a cellular level, focusing on cell proliferation, neural stem cell activation and cell movement. The researchers found a high-proliferation zone in the regenerating spinal cord that shifts over time. They also tracked cells to see how they move into the regenerate. Using a mathematical model, they predicted that the acceleration of the cell cycle is the main driver of spinal cord regeneration in axolotls, with cell influx and neural stem cell activation playing minor roles.

Study Duration

8 days

Participants

8 axolotls, 2–3 cm snout to tail

Evidence Level

Not specified

Key Findings

1
The regenerating spinal cord grows with increasing velocity during the first 8 days.
2
A high-proliferation zone emerges in the regenerating spinal cord at day 4, initially extending 800 mm anterior to the amputation plane.
3
Acceleration of the cell cycle is the major driver of the observed regenerative spinal cord outgrowth.

Research Summary

This study investigates the cellular mechanisms underlying spinal cord regeneration in axolotls, focusing on cell proliferation, neural stem cell activation, and cell influx. The researchers identified a high-proliferation zone that shifts posteriorly over time and quantified cell influx into the regenerate. Using a mathematical model, they concluded that the acceleration of the cell cycle is the major driver of regenerative spinal cord outgrowth, with cell influx and neural stem cell activation playing minor roles.

Practical Implications

Understanding Regeneration

Provides a deeper understanding of spinal cord regeneration in axolotls.

Identifying Key Signals

May help to focus the search for key signals that might be operating in the high-proliferation zone to speed up the cell cycle of regenerative neural stem cells.

Molecular Mechanisms

New insights to help elucidate the molecular mechanisms that drive spontaneous spinal cord regeneration in vivo.

Study Limitations

1
The model does not include the regulation of individual cellular mechanisms and thus it does not consider compensatory mechanisms that may operate under perturbed conditions.
2
The assumption that knocking out Sox2 only affects the acceleration of the cell cycle might not be completely valid.
3
The study focuses primarily on the first 8 days of regeneration, limiting insights into later stages.

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