How a reaction-diffusion signal can control spinal cord regeneration in axolotls: A modeling study

iScience, 2024 · DOI: https://doi.org/10.1016/j.isci.2024.110197 · Published: July 19, 2024

Regenerative Medicine Genetics Bioinformatics

Simple Explanation

Axolotls possess the unique ability to completely regenerate their spinal cord after amputation. This study investigates whether the regeneration-inducing signal follows a reaction-diffusion process using a computational model. A hybrid multi-scale cell-based computational model was developed, combining the ependymal cell layer with a signal that follows a reaction-diffusion scheme while orchestrating the regenerative response by accelerating the ependymal cell cycle. The model showed that the spinal cord growth emerging during regeneration in the axolotl can be controlled by the reaction-diffusion characteristic length and the ependymal cell-to-signal sensitivity.

Study Duration

Not specified

Participants

Computational model validated with experimental data

Evidence Level

Computational Modeling Study

Key Findings

1
Spinal cord regeneration can be explained by a potential signaling mechanism operating under a reaction-diffusion scheme.
2
The evolution of spinal cord outgrowth is controlled by the interplay between the diffusion coefficient and the degradation constant.
3
The regenerative response of the spinal cord can be modulated by the cell sensitivity to the signal.

Research Summary

This theoretical study investigated whether the regeneration-inducing signal can follow a reaction-diffusion process, developing a computational model validated with experimental data. The study demonstrates that control of regenerative response solely relies on cell-to-signal sensitivity and the signal reaction-diffusion characteristic length. The study provides insights into the biophysical properties of signaling processes responsible for successful axolotl spinal cord regeneration.

Practical Implications

Identifies Key Regenerative Factors

Highlights the importance of cell-to-signal sensitivity and the signal's reaction-diffusion characteristic length in controlling spinal cord regeneration.

Provides a Framework for Further Research

Lays the groundwork for future identification of the specific signal that controls spinal cord regeneration.

Explains Regenerative Failure in Sox2 Knockouts

Offers a conceptual framework to interpret the lack of regenerative response in Sox2 knockout axolotls by showing how reduced cell sensitivity to the signal inhibits regeneration.

Study Limitations

1
The 2D model can be reduced to a 1D model due to boundary conditions and cell division rules.
2
The 2D cell-based computational model focuses on the early regenerative response.
3
The theory demonstrates that the regenerative growth scales with the characteristic length of the signal rely on the fast diffusion and reaction approximation.

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