The various routes to functional regeneration in the central nervous system

Communications Biology, 2020 · DOI: https://doi.org/10.1038/s42003-020-0773-z · Published: January 14, 2020

Regenerative Medicine Neurology Genetics

Simple Explanation

The axolotl, a Mexican salamander, possesses remarkable regenerative abilities. After an injury, glial cells near the injury site in axolotls form a signaling heterodimer. This heterodimer is composed of c-Fos and JunB genes, which are also present in humans. Understanding the molecular control of regeneration is crucial for advancing our knowledge at a molecular level. Different species employ diverse mechanisms to achieve regeneration. Studying various research organisms is essential to understand and define the principles of regeneration.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Axolotls activate glial cell division and migration to fill in the missing portion of the neural tube after spinal cord transection, making it impossible to distinguish old from new tissue morphologically.
2
A heterodimer consisting of c-Fos and JunB transiently regulates the GFAP promoter in axolotls, preventing the upregulation of GFAP expression.
3
Overexpression of c-Jun in axolotl glial cells leads to upregulation of GFAP and other genes involved in reactive gliosis, ultimately blocking axon regeneration.

Research Summary

The review explores the diversity of regenerative mechanisms in the central nervous system across different species, focusing on the molecular control of regeneration, particularly in axolotls. It highlights the role of glial cells and the AP-1 transcription factor in spinal cord regeneration, comparing regenerative species like axolotls and lampreys with non-regenerative species like humans. The review also discusses the involvement of the immune system in regeneration and suggests future research directions for developing therapies for spinal cord injury and neurodegenerative diseases.

Practical Implications

Therapeutic Strategies

Understanding the molecular mechanisms of regeneration in species like axolotls can inform the development of therapies for spinal cord injury and neurodegenerative diseases in humans.

Heterodimer Composition

Modifying the composition of the AP-1 heterodimer (e.g., c-Fos:JunB) could potentially alter the glial cell response and promote axon regeneration in mammals after spinal cord injury.

Immune System Modulation

Controlling the timing and duration of immune cell recruitment to the injury site could enhance regenerative outcomes, as observed in zebrafish heart regeneration.

Study Limitations

1
Lack of high-level annotation of many genomes makes it difficult to precisely identify which Fos and Jun family members are activated in regenerative species.
2
The review acknowledges that the exact signaling pathways downstream of the GFAP promoter in axolotl remain to be fully elucidated.
3
The complexity of the immune system's role in regeneration, particularly the timing and duration of immune stimulation, presents a significant challenge.

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