Axon Regeneration Pathways Identified by Systematic Genetic Screening in C. elegans

Lizhen Chen, Zhiping Wang, Anindya Ghosh-Roy, Thomas Hubert, Dong Yan, Sean O'Rourke, Bruce Bowerman, Zilu Wu, Yishi Jin, Andrew D. Chisholm

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1043-1057
Number of pages15
JournalNeuron
Volume71
Issue number6
DOIs
StatePublished - Sep 22 2011

ASJC Scopus subject areas

  • Neuroscience(all)

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