Axon Regeneration

[size=12pt]Axon Regeneration Pathways Identified by Systematic Genetic Screening in C. elegans[/size]
Lizhen Chen, Zhiping Wang, Anindya Ghosh-Roy, Thomas Hubert, Dong Yan, Sean O'Rourke, Bruce Bowerman, Zilu Wu1, Yishi Jin, Andrew D. Chisholm

Purchase
1 Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA
2 Howard Hughes Medical Institute
3 Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA
4 Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Accepted 5 July 2011. Published: September 21, 2011. Available online 21 September 2011.

Summary
The mechanisms underlying the ability of axons to regrow after injury remain poorly explored at the molecular genetic level. We used a laser injury model in Caenorhabditis elegans mechanosensory neurons to screen 654 conserved genes for regulators of axonal regrowth. We uncover several functional clusters of genes that promote or repress regrowth, including genes classically known to affect axon guidance, membrane excitability, neurotransmission, and synaptic vesicle endocytosis. The conserved Arf Guanine nucleotide Exchange Factor (GEF), EFA-6, acts as an intrinsic inhibitor of regrowth. By combining genetics and in vivo imaging, we show that EFA-6 inhibits regrowth via microtubule dynamics, independent of its Arf GEF activity. Among newly identified regrowth inhibitors, only loss of function in EFA-6 partially bypasses the requirement for DLK-1 kinase. Identification of these pathways significantly expands our understanding of the genetic basis of axonal injury responses and repair.

www.sciencedirect.com/science/article/pii/S0896627311006064