Glial Cell-Axonal Growth Cone Interactions in Neurodevelopment and Regeneration

Frontiers in Neuroscience, 2020 · DOI: 10.3389/fnins.2020.00203 · Published: March 10, 2020

Simple Explanation

The developing nervous system relies on intricate interactions between neurons and glial cells to guide axons to their correct destinations. Glial cells communicate with growth cones either directly through cell contacts or by modifying the local environment. Different glial cell types, including microglia, oligodendrocytes, astrocytes, and Schwann cells, can influence axon growth and guidance. Understanding these interactions may lead to therapies for modulating neuron growth during development or regeneration after injury. This review focuses on how glial cells directly interact with growing axons to influence neuronal connectivity, with a particular focus on regeneration after spinal cord injury. A better understanding of the roles of glia in neurodevelopment can inform strategies to improve axon regeneration after injury.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Astrocytes, through cellular processes, directly interact with growing axons, with these interactions depending on cell adhesion molecules like NCAM and N-cadherin. Distinct astrocyte populations can have differential effects on axon development, either promoting or inhibiting neurite growth.
2
Oligodendrocytes and their precursor cells (OPCs) generally inhibit axon growth through molecules like Nogo and MAG. NG2, expressed by OPCs during neurodevelopment, also has an inhibitory effect on axon growth.
3
Microglia play a role in limiting axon outgrowth and interneuron distribution during development. Microglial activation can be inhibitory to axon growth and guidance, expressing repulsive guidance molecule a (RGMa).

Research Summary

Glial cells play critical roles in axon growth and guidance during neurodevelopment, influencing neuronal wiring and impacting outcomes in conditions like spinal cord injury. Understanding the molecular mechanisms of glial-axon interactions, involving cell adhesion molecules and repulsive guidance cues, is crucial for developing effective regenerative therapies. Modulating glial cell activity and reprogramming their molecular properties hold promise for promoting axon regeneration and functional recovery after CNS and PNS injuries.

Practical Implications

Therapeutic Targets

Identifying specific molecules involved in glial-axon interactions, such as RGMa, Nogo, and specific integrins, can provide targets for therapeutic interventions to promote axon regeneration.

Cell-Based Therapies

Transplantation of growth-promoting glial cells like olfactory ensheathing cells (OECs) and neural stem cells (NSCs) can provide a supportive environment for axon regeneration after injury.

Drug Development

Developing drugs that modulate glial cell activity, such as minocycline for reducing RGMa expression or antibodies neutralizing Nogo-A, can promote axon growth and functional recovery.

Study Limitations

1
The complexity of glial-axon interactions and the diverse functions of different glial subtypes make it challenging to develop targeted therapies.
2
Translating findings from in vitro and animal studies to human clinical trials can be difficult due to differences in the nervous system and injury responses.
3
Further research is needed to fully elucidate the molecular mechanisms and signaling pathways involved in glial-axon interactions during neurodevelopment and regeneration.

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