Different Fgfs have distinct roles in regulating neurogenesis after spinal cord injury in zebrafish

Neural Development, 2018 · DOI: https://doi.org/10.1186/s13064-018-0122-9 · Published: November 8, 2018

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates how different types of fibroblast growth factors (Fgfs) affect nerve cell regeneration after spinal cord injury in zebrafish. Zebrafish can regenerate their spinal cords, unlike mammals. The researchers looked at specific Fgf members and their receptors to see how they influence nerve development and regeneration at different times after a spinal cord injury. They found that Fgf3 helps create new motor neurons and build axons, while other Fgfs like Fgf2 and Fgf8 have different roles during development. These findings suggest that Fgf type, age, timing, and neuronal population requirements could be tailored to improve regenerative processes.

Study Duration

Not specified

Participants

Adult zebrafish (3-6 months old), zebrafish embryos, mammalian PC12 cells

Evidence Level

Not specified

Key Findings

1
Fgf3 drives neurogenesis of Islet1 expressing motor neuron subtypes and mediate axonogenesis in cMet expressing motor neuron subtypes.
2
During development Fgf2, Fgf3 and Fgf8 mediate neurogenesis of Islet1 expressing neurons and neuronal sprouting of both, Islet1 and cMet expressing motor neurons.
3
In mammalian PC12 cells, all three Fgfs increased cell proliferation, however, only Fgf2 and to some extent Fgf8, but not Fgf3 facilitated neurite outgrowth.

Research Summary

This study examines the roles of different Fgf members and their receptors in neurogenesis and regeneration following spinal cord injury (SCI) in zebrafish, comparing these roles to those during development and in mammalian cell culture. The findings indicate that Fgf3 specifically promotes the neurogenesis of Islet1-expressing motor neurons and axonogenesis in cMet-expressing motor neurons after SCI. During development, Fgf2, Fgf3, and Fgf8 all mediate neurogenesis of Islet1 neurons and sprouting of both Islet1 and cMet motor neurons. Experiments with mammalian PC12 cells showed that while all three Fgfs increased cell proliferation, only Fgf2 and, to a lesser extent, Fgf8, facilitated neurite outgrowth, highlighting differential roles of Fgfs during neural development and regeneration.

Practical Implications

Therapeutic Targeting

Targeting specific Fgf ligands and receptors could improve motor neuron regeneration after spinal cord injury.

Age-Dependent Strategies

Regenerative strategies may need to be tailored based on the age of the organism to account for functional switches in Fgf signaling.

Combined Therapies

Combining different Fgfs or Fgf-related factors may be necessary to drive all required regenerative processes, such as neural proliferation and neurite outgrowth.

Study Limitations

1
The study primarily uses a zebrafish model, and results may not directly translate to mammals.
2
The specific mechanisms by which Fgf receptors mediate neurogenesis at different timepoints post-SCI are not fully elucidated.
3
Additional delivery or stability issues of injected Fgf8

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