Chx10+V2a interneurons in spinal motor regulation and spinal cord injury

Neural Regeneration Research, 2023 · DOI: https://doi.org/10.4103/1673-5374.355746 · Published: October 10, 2022

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Chx10+V2a spinal interneurons play a vital role in controlling motoneurons, which are essential for movement. These interneurons are important for starting, maintaining, and coordinating locomotion. Understanding their function could lead to new treatments for spinal cord injuries. This review focuses on how Chx10+V2a interneurons develop, their characteristics, and their roles, especially in the context of spinal cord injury. It explores how these cells are integrated into various spinal circuits to facilitate movement and other functions. Recent research is exploring the potential of transplanting or stimulating Chx10+V2a interneurons as a way to treat spinal cord injuries. Optimizing the survival and integration of these cells after transplantation is a key focus for future therapeutic strategies.

Study Duration

Searches performed from January 2000 to March 2022

Participants

Not specified

Evidence Level

Review

Key Findings

1
Chx10+V2a interneurons originate from the p2 progenitor domain and are directed by Notch and TGF-β signals, which suppress motoneuron fates, ensuring the appropriate balance of V2a/V2b commitment through transcription factors.
2
Anatomical studies reveal that Chx10+V2a interneurons are located in spinal cord lamina VII, providing ipsilateral glutamatergic input to motoneurons, V0 interneurons, and inhibitory interneurons, receiving input from various sources to refine their output.
3
Chx10+V2a interneurons are crucial in pathological changes during spinal injury/degeneration, with current therapeutic strategies involving transplantation techniques using cells derived from various stem cell sources, aiming to improve survival, migration, and functional integration.

Research Summary

This review summarizes the regulatory role of Chx10-expressing V2a spinal interneurons in spinal locomotion and spinal cord disease, noting their origin in the p2 progenitor domain and induction by Notch and TGF-β signals, inhibiting MN fates. Chx10+V2a interneurons, located in spinal cord lamina VII, provide glutamatergic input to MNs, V0 interneurons, and inhibitory interneurons, receiving input from various sources to refine output and playing functional roles in movement initiation and regulation. Chx10+V2a interneurons play a crucial role in pathological changes during spinal injury/degeneration; current therapeutic strategies use transplantation techniques with stem cell-derived interneurons, aiming to improve survival, migration, and functional integration.

Practical Implications

Therapeutic Target

V2a interneurons may be a potential key therapeutic target for neurodegenerative or spinal injury disease.

Clinical Application Challenges

Persisting challenges for the clinical application of V2a interneuron therapies include the lack of a comprehensive framework to address the diverse action of V2a interneurons across spinal segments.

Future Research

Emerging technologies, including optogenetics, chemogenetic ablation, and single-cell sequencing, hold promising possibilities to define the mechanism of V2a interneurons more comprehensively.

Study Limitations

1
Effectiveness of stimulation/transplantation of Chx10+V2a interneurons in SCI treatment cannot be fully verified owing to the differences between humans and other animals used in preclinical studies.
2
There is no clinical report suggesting that treatment with Chx10+V2a interneurons is associated with clinical improvements in patients with neurological disorders.
3
Current methods for primary culture of Chx10+V2a interneurons are inadequate to produce a sufficient number of cells to be utilized in a clinical study.

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