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  4. Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration

Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration

eLife, 2021 · DOI: https://​doi.​org/​10.​7554/​eLife.​55665 · Published: May 14, 2021

Regenerative MedicineGeneticsBioinformatics

Simple Explanation

Axolotls can regenerate their spinal cords after injury. This study investigates how cell proliferation is controlled during this regeneration process. The researchers developed a model and an imaging tool to understand the timing and location of cell division during spinal cord regeneration in axolotls. The study combines mathematical modeling with experimental data. They created a new transgenic axolotl line called AxFUCCI that allows them to visualize cell cycle phases in living tissue. This helps to understand the signals that drive successful spinal cord regeneration. The research showed that a signal recruits ependymal cells within a specific distance from the injury site during a specific time window, leading to accelerated cell cycles and spinal cord outgrowth. They also found evidence of cell cycle synchrony among ependymal cells during regeneration.

Study Duration
5 days
Participants
Axolotls (Ambystoma mexicanum)
Evidence Level
Experimental and computational modeling

Key Findings

  • 1
    Spinal cord regeneration is consistent with a signal that recruits ependymal cells during approximately 85 hours after amputation within approximately 830 μm of the injury.
  • 2
    The FUCCI axolotls confirmed the predicted appearance time and size of the injury-induced recruitment zone and revealed cell cycle synchrony between ependymal cells.
  • 3
    Shortening of the S phase of the cell cycle is sufficient to explain the initial regenerative spinal cord outgrowth.

Research Summary

This study investigates the mechanisms underlying spinal cord regeneration in axolotls, focusing on the spatiotemporal pattern of cell proliferation. It demonstrates that the regenerative response is consistent with a signal that recruits ependymal cells within a specific time and distance from the injury. The researchers developed AxFUCCI axolotls to visualize cell cycles in vivo, confirming the predicted appearance time and size of the recruitment zone and revealing cell cycle synchrony between ependymal cells. Modeling and experimental results indicate that a signal acts during approximately 85 hours following amputation, recruiting cells within approximately 828 μm of the amputation plane, and that S phase shortening plays a key role in initial spinal cord outgrowth.

Practical Implications

Targeted Therapies

Identifying the injury signal could lead to therapies that stimulate regeneration in humans with spinal cord injuries.

Understanding Cell Cycle Control

The findings on cell cycle synchrony and phase shortening provide insights into the fundamental mechanisms controlling cell proliferation during regeneration.

Drug discovery

AxFUCCI axolotls can serve as useful tools for future studies of proliferation during development and regeneration.

Study Limitations

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