Dynamic expression of Slit1–3 and Robo1–2 in the mouse peripheral nervous system after injury

Neural Regen Res, 2020 · DOI: 10.4103/1673-5374.268930 · Published: November 8, 2019

Regenerative Medicine Neurology Genetics

Simple Explanation

The study investigates how the expression of Slit1-3 and Robo1-2 changes in the mouse peripheral nervous system after a sciatic nerve injury. These molecules are known to guide axons during nervous system development. Researchers found that after nerve injury, the expression of these molecules changes dynamically in different parts of the peripheral nervous system, including the spinal cord, dorsal root ganglia, and sciatic nerve. The findings suggest that Slit3, a specific molecule in this family, and its receptor Robo1 could play a key role in the repair process of peripheral nerves after injury.

Study Duration

14 Days

Participants

15 male and 15 female C57BL/6 mice (20–25 g) and nine male PLP-GFP mice (20–25 g)

Evidence Level

Not specified

Key Findings

1
In the dorsal root ganglion (DRG), Slit1-3 and Robo1-2 mRNA expression were initially downregulated within 4 days after injury, but Slit1-3 mRNA expression remained upregulated during regeneration from 4-14 days after injury.
2
In the sciatic nerve, Slit1, Slit2, and Robo2 were barely detectable in the nerve bridge and distal nerve stump within 14 days after injury, while Slit3 was highly expressed in macrophages surrounding the nerve bridge.
3
Robo1 was upregulated in vimentin-positive cells and migrating Schwann cells inside the nerve bridge, and also upregulated in Schwann cells of the distal nerve stump within 14 days after injury.

Research Summary

This study examined the expression of Slit1–3 and Robo1–2 in the adult mouse peripheral nervous system after sciatic nerve transection injury using qRT-PCR, western blot, and immunostaining. The study found that Slit1–3 and Robo1–2 are expressed in spinal cord motor neurons and DRG sensory neurons after mouse sciatic nerve injury. The results indicate that the Slit3/Robo signaling pathway may play an important role in peripheral nerve regeneration, with Slit3 being the major ligand expressed in the nerve bridge and distal nerve stump.

Practical Implications

Targeted Therapies

Slit3 could be delivered into the wall of nerve guidance conduits to control precise axon re-targeting for peripheral nerve repair.

Understanding Axon Guidance

The identification of Slit3 as a major ligand in the nerve bridge and distal nerve stump provides insights into axon guidance during peripheral nerve regeneration.

Cell-Specific Interactions

Further research can focus on the interactions between Slit3 and Robo1/2 in specific cell types (macrophages, Schwann cells, and vimentin-positive cells) to understand their roles in nerve repair.

Study Limitations

1
The study was unable to identify the cell type that was Robo1 and vimentin double-positive in the nerve bridge.
2
The function of Slit/Robo signaling in peripheral nerve regeneration was not further investigated in this study.
3
A major limitation for this study is that we were unable to identify the cell type that was Robo1 and vimentin double-positive in the nerve bridge because of a lack of cell markers to label this population of migrating cells.

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