Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS in Drosophila

eLife, 2020 · DOI: https://doi.org/10.7554/eLife.57395 · Published: October 6, 2020

Simple Explanation

The study uses optogenetics to investigate neuronal repair in fruit fly larvae. Light-sensitive proteins are fused to signaling proteins, allowing light to activate regeneration programs in neurons. A laser damages a neuron in a genetically modified larva, and dim blue light activates the regeneration program. This allows the neuron to repair itself and guides its regeneration. By focusing the blue light on the damaged end, the direction of the cell’s growth is guided during regeneration.

Study Duration

Not specified

Participants

Drosophila larvae

Evidence Level

Not specified

Key Findings

1
OptoRaf or optoAKT activation enhanced axon regeneration in both regeneration-competent and -incompetent sensory neurons in the peripheral nervous system.
2
optoRaf and optoAKT differ in their signaling kinetics during regeneration, showing a gated versus graded response, respectively.
3
Activation of optoRaf or optoAKT promotes axon regeneration and functional recovery in the CNS.

Research Summary

The study uses optogenetic systems, optoRaf and optoAKT, to delineate the contribution of the ERK and AKT signaling pathways to neuroregeneration in live Drosophila larvae. optoRaf or optoAKT activation not only enhanced axon regeneration in both regeneration-competent and -incompetent sensory neurons in the peripheral nervous system but also allowed temporal tuning and proper guidance of axon regrowth. their activation promotes axon regrowth and functional recovery of the thermonociceptive behavior. We conclude that non-neuronal optogenetics targets damaged neurons and signaling subcircuits, providing a novel strategy in the intervention of neural damage with improved precision.

Practical Implications

Targeted Neural Repair

Optogenetics allows for precise targeting of individual damaged cells, reducing side effects and improving treatment efficacy.

Understanding Repair Signals

The combination of light and genetics can reveal more about how repair signals work, leading to a better understanding of neuroregeneration.

Future Mammalian Research

Further research into LEDs that can be implanted may be necessary before neuronal repair experiments can be performed in mammals.

Study Limitations

1
Blue light does not penetrate well into mammalian tissues.
2
The regeneration programs in flies and mammals may not be completely identical.
3
Intact optogenetics in larger mammals is limited by the poor penetration depth of blue light

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