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In Situ Visualization of Axon Growth and Growth Cone Dynamics in Acute Ex Vivo Embryonic Brain Slice Cultures
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A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury
Marta Koch1,2, Maya Nicolas1,2, Marlen Zschaetzsch1,2
1Laboratory of Neurogenetics, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium.
Frontiers in Cellular Neuroscience
|February 24, 2018
Summary
Researchers identified a novel signaling pathway involving Dscam1, Faf/Usp9x, and Kayak/Fos that promotes axonal regeneration after central nervous system (CNS) injury. This discovery offers potential therapeutic targets for restoring function after nerve trauma.
Area of Science:
- Neuroscience
- Molecular Biology
- Regenerative Medicine
Background:
- Adult central nervous system (CNS) injuries lead to permanent disability due to the failure of severed axons to regenerate.
- Identifying molecular regulators that promote intrinsic axonal growth is crucial for developing strategies to restore CNS function after trauma.
Purpose of the Study:
- To conduct a gain-of-function genetic screen in Drosophila to identify potent inducers of axonal regeneration following injury.
- To elucidate a novel signaling pathway involving Down Syndrome Cell Adhesion Molecule (Dscam1), Fat Facets (Faf)/Usp9x, and Kayak (Kay)/Fos in axonal growth.
Main Methods:
- Utilized a gain-of-function genetic screen in Drosophila to identify genes promoting axonal regrowth.
- Performed genetic and biochemical analyses to establish the functional relationships between Dscam1, Faf/Usp9x, and the JNK pathway transcription factor Kayak/Fos.
Main Results:
- Identified a novel signaling axis: Faf/Usp9x stabilizes Dscam1 protein levels by acting on its mRNA's 3'-UTR.
- Demonstrated that Dscam1 functions upstream of the growth-promoting Jun N-Terminal Kinase (JNK) pathway.
- Showed that the mammalian homolog of Faf, Usp9x/FAM, possesses conserved Dscam1-stabilizing and regenerative activities.
Conclusions:
- A conserved signaling pathway involving Faf/Usp9x, Dscam1, and the JNK pathway promotes axonal regeneration.
- This pathway represents a promising target for therapeutic interventions aimed at enhancing CNS repair and functional recovery after injury.
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