DUSP2 deletion with CRISPR/Cas9 promotes Mauthner cell axonal regeneration at the early stage of zebrafish

Neural Regeneration Research, 2023 · DOI: https://doi.org/10.4103/1673-5374.350208 · Published: March 1, 2023

Regenerative Medicine Neurology Genetics

Simple Explanation

After a CNS injury, axon regeneration is vital for recovery. This study identifies DUSP2 as a negative regulator of axon regeneration in Mauthner cells (M-cells) of zebrafish. By knocking out the dusp2 gene using CRISPR/Cas9, the researchers observed enhanced M-cell axon regeneration in zebrafish larvae within 8 days after birth. The study suggests that DUSP2 knockout promotes axon regeneration by increasing JNK phosphorylation, a key signaling pathway involved in nerve regeneration.

Study Duration

8 days

Participants

Zebrafish larvae

Evidence Level

Level III, Experimental Study

Key Findings

1
DUSP2 knockout in zebrafish promotes M-cell axon regeneration at an early stage after birth (within 8 days).
2
Overexpression of DUSP2 in zebrafish retards the regeneration of M-cell axons.
3
DUSP2 knockout increases the levels of phosphorylated JNK, suggesting a mechanism through enhancing JNK phosphorylation.

Research Summary

This study investigates the role of DUSP2, a phosphatase, in axon regeneration of Mauthner cells (M-cells) in zebrafish after spinal cord injury. The researchers used CRISPR/Cas9 to knock out the dusp2 gene and observed that M-cell axons in dusp2–/– zebrafish exhibited better regeneration at the early stage after birth. The study suggests that DUSP2 negatively regulates axon regeneration, possibly by modulating JNK phosphorylation levels.

Practical Implications

Potential Therapeutic Target

DUSP2 could be a potential therapeutic target for promoting axon regeneration after spinal cord injury.

JNK Pathway Modulation

Modulating the JNK phosphorylation pathway by targeting DUSP2 could enhance nerve regeneration.

Early Intervention

Interventions targeting DUSP2 might be most effective in the early stages after nerve injury.

Study Limitations

1
The study focuses on the early stages of regeneration (within 8 days of birth).
2
The exact contribution of JNK1, JNK2, and JNK3 subtypes requires further clarification.
3
Additional studies are needed to strengthen the involvement of JNK and ATF3 in the role of DUSP2.

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