title: EFN-4 functions in LAD-2-mediated axon guidance in Caenorhabditis elegans.
abstract: During development of the nervous system, growing axons rely on guidance molecules to direct axon pathfinding. A well-characterized family of guidance molecules are the membrane-associated ephrins, which together with their cognate Eph receptors, direct axon navigation in a contact-mediated fashion. InC. elegans, the ephrin-Eph signaling system is conserved and is best characterized for their roles in neuroblast migration during early embryogenesis. This study demonstrates a role for the C. elegans ephrin EFN-4 in axon guidance. We provide both genetic and biochemical evidence that is consistent with the C. elegans divergent L1 cell adhesion molecule LAD-2 acting as a non-canonical ephrin receptor to EFN-4 to promote axon guidance. We also show that EFN-4 probably functions as a diffusible factor because EFN-4 engineered to be soluble can promote LAD-2-mediated axon guidance. This study thus reveals a potential additional mechanism for ephrins in regulating axon guidance and expands the repertoire of receptors by which ephrins can signal.
authors.affiliation: Department of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Bingyun
authors.initials: B
authors.lastname: Dong
authors.affiliation: Department of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, MN 55455, USA Developmental Biology Center, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Melinda
authors.initials: M
authors.lastname: Moseley-Alldredge
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, GA 30144, USA.
authors.forename: Alicia A
authors.initials: AA
authors.lastname: Schwieterman
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, GA 30144, USA.
authors.forename: Cory J
authors.initials: CJ
authors.lastname: Donelson
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, GA 30144, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: McMurry
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, GA 30144, USA.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hudson
authors.affiliation: Department of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, MN 55455, USA Developmental Biology Center, University of Minnesota, Minneapolis, MN 55455, USA chenx260@umn.edu.
authors.forename: Lihsia
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002460:Cell Line; D036342:Ephrins / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D009024:Morphogenesis; D009420:Nervous System / Q000196:embryology*; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics*; D055495:Neurogenesis / Q000502:physiology*; D036081:Receptors, Eph Family / Q000235:genetics; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; C470369:EFN-4 protein, C elegans; D036342:Ephrins; C526374:LAD-2 protein, C elegans; D008565:Membrane Proteins; D039842:Neural Cell Adhesion Molecule L1; D036081:Receptors, Eph Family; D008666:Metalloendopeptidases; C109978:SUP-17 protein, C elegans
keywords: Axon guidance; C. elegans; Ephrin; L1CAM