title: Characterization of loss-of-function and gain-of-function Eph receptor tyrosine kinase signaling in C. elegans axon targeting and cell migration.
abstract: To understand how our brains function, it is necessary to know how neurons position themselves and target their axons and dendrites to their correct locations. Several evolutionarily conserved axon guidance molecules have been shown to help navigate axons to their correct target site. The Caenorhabditis elegans Eph receptor tyrosine kinase (RTK), VAB-1, has roles in early neuroblast and epidermal cell movements, but its roles in axon guidance are not well understood. Here, we report that mutations that disrupt the VAB-1 Eph receptor tyrosine kinase cause incompletely penetrant defects in axonal targeting and neuronal cell body positioning. The predominant axonal defect in vab-1 mutant animals was an overextension axon phenotype. Interestingly, constitutively active VAB-1 tyrosine kinase signaling caused a lack of axon outgrowth or an early termination phenotype, opposite to the loss-of-function phenotype. The combination of loss-of-function and gain-of-function analyses suggests that the VAB-1 Eph RTK is required for targeting or limiting axons and neuronal cells to specific regions, perhaps by transducing a repellent or stop cue.
authors.affiliation: Department of Biology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Mohamed
authors.forename: Ian D
authors.initials: ID
authors.lastname: Chin-Sang
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D036342:Ephrins / Q000378:metabolism; D009154:Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D036081:Receptors, Eph Family / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D036342:Ephrins; D020794:Receptor Protein-Tyrosine Kinases; D036081:Receptors, Eph Family; C111040:vab-1 protein, C elegans