title: Axon regeneration pathways identified by systematic genetic screening in C. elegans.
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.
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Chen
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Wang
authors.forename: Anindya
authors.initials: A
authors.lastname: Ghosh-Roy
authors.forename: Thomas
authors.initials: T
authors.lastname: Hubert
authors.forename: Dong
authors.initials: D
authors.lastname: Yan
authors.forename: Sean
authors.initials: S
authors.lastname: O'Rourke
authors.forename: Bruce
authors.initials: B
authors.lastname: Bowerman
authors.forename: Zilu
authors.initials: Z
authors.lastname: Wu
authors.forename: Yishi
authors.initials: Y
authors.lastname: Jin
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Chisholm
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000235:genetics* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D004705:Endocytosis; D005820:Genetic Testing / Q000379:methods*; D005810:Multigene Family; D009154:Mutation; D009416:Nerve Regeneration / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C554747:EFA-6 protein, C elegans