RRC ID 46048
Author Chen L, Wang Z, Ghosh-Roy A, Hubert T, Yan D, O'Rourke S, Bowerman B, Wu Z, Jin Y, Chisholm AD.
Title Axon regeneration pathways identified by systematic genetic screening in C. elegans.
Journal Neuron
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.
Volume 71(6)
Pages 1043-57
Published 2011-9-22
DOI 10.1016/j.neuron.2011.07.009
PII S0896-6273(11)00606-4
PMID 21943602
PMC PMC3183436
MeSH Animals Axons / physiology* Caenorhabditis elegans / anatomy & histology Caenorhabditis elegans / genetics* Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Endocytosis Genetic Testing / methods* Multigene Family Mutation Nerve Regeneration / physiology* Synaptic Vesicles / metabolism
IF 14.415
Times Cited 109
C.elegans tm2124 tm3124