Axon regeneration pathways identified by systematic genetic screening in C. elegans.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Chen, L; Wang, Z; Ghosh-Roy, A; Hubert, T; Yan, D; O'Rourke, S; Bowerman, B; Wu, Z; Jin, Y; Chisholm, AD

Published Date

  • September 22, 2011

Published In

Volume / Issue

  • 71 / 6

Start / End Page

  • 1043 - 1057

PubMed ID

  • 21943602

Pubmed Central ID

  • 21943602

Electronic International Standard Serial Number (EISSN)

  • 1097-4199

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2011.07.009

Language

  • eng

Conference Location

  • United States