The Nogo-66 Receptors NgR1 and NgR3 Are Required for Commissural Axon Pathfinding

The Journal of Neuroscience, 2022 · DOI: https://doi.org/10.1523/JNEUROSCI.1390-21.2022 · Published: May 18, 2022

Regenerative Medicine Neurology Genetics

Simple Explanation

This study investigates the roles of Nogo-66 receptors (NgR1 and NgR3) in guiding commissural axons during the development of the chicken spinal cord. The researchers found that both NgR1 and NgR3 are necessary for commissural axons to cross the midline of the spinal cord and then turn rostrally along the longitudinal axis. Furthermore, the study reveals that NgR1, but not NgR3, interacts with PlexinA2, another protein involved in axon guidance, to regulate this process.

Study Duration

Not specified

Participants

Chicken embryos

Evidence Level

In vivo experimental study

Key Findings

1
Loss of either NgR1 or NgR3 causes commissural axons to stall in the midline area and interferes with the rostral turn of postcrossing axons in the developing chicken spinal cord.
2
NgR1, but not NgR3, requires neuronal PlexinA2 for the regulation of commissural axon guidance, suggesting a cooperative interaction between these two proteins.
3
Downregulation of NgR1 leads to an increase in the phosphorylation of collapsin response mediator protein 2 (CRMP2), implicating CRMP2 phosphorylation in the observed axon guidance defects.

Research Summary

The study demonstrates that NogoA, an NgR1 ligand, regulates commissural axon guidance in the chicken spinal cord. Live imaging shows that interfering with the Nogo/NgR1 pathway alters commissural axon guidance. NgR1 and NgR3 are expressed in dorsal commissural neurons during spinal cord development. Downregulation of either NgR1 or NgR3 interferes with the normal pathfinding of dI1 axons at the floorplate. NgR1 regulates axon guidance by cooperating with neuronal PlexinA2. This interaction affects CRMP2 phosphorylation, ultimately influencing axon turning at the midline.

Practical Implications

Understanding Neural Development

The findings contribute to a better understanding of the molecular mechanisms governing axon guidance during neural development.

Potential Therapeutic Targets

Identifying NgR1, NgR3, and PlexinA2 as key regulators of axon guidance may offer potential therapeutic targets for treating spinal cord injuries or other neurological disorders.

Link Between Development and Regeneration

The study provides a link between neural regenerative mechanisms and developmental processes, suggesting that insights from developmental biology can inform strategies for promoting axon regeneration in the injured adult CNS.

Study Limitations

1
The study focuses on the chicken spinal cord, and the findings may not be directly applicable to other species.
2
The precise mechanisms by which NgR3 regulates axon guidance remain unclear, as it does not appear to require PlexinA2.
3
The study does not fully elucidate the downstream signaling pathways activated by NgR1 and NgR3, and further research is needed to identify all the relevant intracellular mediators.

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