title: Axon response to guidance cues is stimulated by acetylcholine in Caenorhabditis elegans.
abstract: Gradients of acetylcholine can stimulate growth cone turning when applied to neurons grown in culture, and it has been suggested that acetylcholine could act as a guidance cue. However, the role acetylcholine plays in directing axon migrations in vivo is not clear. Here, we show that acetylcholine positively regulates signaling pathways that mediate axon responses to guidance cues in Caenorhabditis elegans. Mutations that disrupt acetylcholine synthesis, transportation, and secretion affect circumferential axon guidance of the AVM neuron and in these mutants exogenously supplied acetylcholine improves AVM circumferential axon guidance. These effects are not observed for the circumferential guidance of the DD and VD motor neuron axons, which are neighbors of the AVM axon. Circumferential guidance is directed by the UNC-6 (netrin) and SLT-1 (slit) extracellular cues, and exogenously supplied acetylcholine can improve AVM axon guidance in mutants when either UNC-6- or SLT-1-induced signaling is disrupted, but not when both signaling pathways are perturbed. Not in any of the mutants does exogenously supplied acetylcholine improve DD and VD axon guidance. The ability of acetylcholine to enhance AVM axon guidance only in the presence of either UNC-6 or SLT-1 indicates that acetylcholine potentiates UNC-6 and SLT-1 guidance activity, rather than acting itself as a guidance cue. Together, our results show that for specific neurons acetylcholine plays an important role in vivo as a modulator of axon responses to guidance cues.
authors.affiliation: Department of Pathology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Xing-Cong
authors.initials: XC
authors.lastname: Ren
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Quinn
authors.forename: William G
authors.initials: WG
authors.lastname: Wadsworth
mesh_terms: D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D003463:Cues; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism; D009068:Movement / Q000187:drug effects; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000075385:Netrins; D011978:Receptors, Nicotinic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; D000075385:Netrins; D011978:Receptors, Nicotinic; C078146:UNC-6 protein, C elegans; C492285:slt-1 protein, C elegans; D000109:Acetylcholine