Rassf7a promotes spinal cord regeneration and controls spindle orientation in neural progenitor cells

EMBO Reports, 2023 · DOI: 10.15252/embr.202254984 · Published: November 21, 2022

Regenerative Medicine Neurology Genetics

Simple Explanation

Spinal cord injuries can lead to lasting disabilities because mammals lack the ability to regrow damaged nerve fibers or generate new spinal neurons at the injury site. Understanding how neural progenitor cells multiply and specialize is essential for figuring out how the spinal cord regenerates after an injury. Compared to mammals, zebrafish have a strong ability to regenerate their spinal cords. This study shows that a protein called Rassf7a helps zebrafish spinal cords regenerate after injury. Zebrafish larvae with a mutated version of the rassf7a gene showed defects in spinal cord regeneration and spinal neurogenesis. Live imaging revealed abnormal asymmetric neurogenic divisions and spindle orientation defects in mutant neural progenitor cells. Rassf7a is mainly found in neural progenitor cells and is essential for cell cycle progression. The data indicates that Rassf7a plays a role in controlling spindle orientation and the growth of neural progenitor cells after spinal cord injury.

Study Duration

Not specified

Participants

Zebrafish larvae and hTERT-RPE-1 cells

Evidence Level

Not specified

Key Findings

1
Rassf7a promotes spinal cord regeneration in zebrafish. Zebrafish larvae with a rassf7a mutation exhibit defects in spinal cord regeneration and spinal neurogenesis.
2
Rassf7a regulates spindle orientation during radial glia proliferation. Live imaging shows abnormal asymmetric neurogenic divisions and spindle orientation defects in mutant neural progenitor cells.
3
Rassf7a is mainly expressed in neural progenitor cells and localizes to the centrosome. It is essential for cell cycle progression, suggesting its role in modulating the proliferation of neural progenitor cells after spinal cord injury.

Research Summary

This study investigates the role of Rassf7a, a member of the Ras-association domain family, in spinal cord regeneration in zebrafish. The researchers found that zebrafish rassf7a mutants displayed significant regeneration defects after spinal cord injury, mainly due to restricted cell proliferation of neural progenitor cells. The study provides data showing that rassf7a encodes a centrosomal protein and regulates spindle orientation during radial glia proliferation. These results suggest an important role of Rassf7a in spinal cord regeneration of zebrafish larvae after injury. The findings may contribute to understanding the reasons for the failure of axonal regeneration in mammals, potentially leading to improved strategies for treating spinal cord injuries.

Practical Implications

Therapeutic Potential

Understanding the role of Rassf7a in spinal cord regeneration could lead to novel therapeutic strategies for spinal cord injuries in mammals, including humans.

Drug Development

Identifying the molecular mechanisms by which Rassf7a regulates spindle orientation and cell proliferation could provide targets for drug development aimed at promoting spinal cord regeneration.

Cell Transplantation Improvement

Enhancing the expression or activity of Rassf7a in transplanted neural progenitor cells may improve their regenerative capacity in spinal cord injury models.

Study Limitations

1
The study is primarily conducted in zebrafish larvae, and the findings may not be directly transferable to mammals due to differences in spinal cord regeneration mechanisms.
2
The specific molecular mechanisms by which Rassf7a regulates spindle orientation and cell proliferation are not fully elucidated.
3
The potential redundancy of other RASSF family proteins in compensating for the loss of Rassf7a function is not fully explored.

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