title: The Caenorhabditis elegans Ephrin EFN-4 Functions Non-cell Autonomously with Heparan Sulfate Proteoglycans to Promote Axon Outgrowth and Branching.
abstract: The Eph receptors and their cognate ephrin ligands play key roles in many aspects of nervous system development. These interactions typically occur within an individual tissue type, serving either to guide axons to their terminal targets or to define boundaries between the rhombomeres of the hindbrain. We have identified a novel role for the Caenorhabditis elegans ephrin EFN-4 in promoting primary neurite outgrowth in AIY interneurons and D-class motor neurons. Rescue experiments reveal that EFN-4 functions non-cell autonomously in the epidermis to promote primary neurite outgrowth. We also find that EFN-4 plays a role in promoting ectopic axon branching in a C. elegans model of X-linked Kallmann syndrome. In this context, EFN-4 functions non-cell autonomously in the body-wall muscle and in parallel with HS modification genes and HSPG core proteins. This is the first report of an epidermal ephrin providing a developmental cue to the nervous system.
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, Georgia 30144.
authors.forename: Alicia A
authors.initials: AA
authors.lastname: Schwieterman
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, Georgia 30144.
authors.forename: Alyse N
authors.initials: AN
authors.lastname: Steves
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California 95064.
authors.forename: Vivian
authors.initials: V
authors.lastname: Yee
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, Georgia 30144.
authors.forename: Cory J
authors.initials: CJ
authors.lastname: Donelson
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, Georgia 30144.
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Bentley
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, Georgia 30144.
authors.forename: Elise M
authors.initials: EM
authors.lastname: Santorella
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, Georgia 30144.
authors.forename: Taylor V
authors.initials: TV
authors.lastname: Mehlenbacher
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, Georgia 30144.
authors.forename: Aaron
authors.initials: A
authors.lastname: Pital
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, Georgia 30144.
authors.forename: Austin M
authors.initials: AM
authors.lastname: Howard
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, Georgia 30144.
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Wilson
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, Georgia 30144.
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Ereddia
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045.
authors.forename: Kelsie S
authors.initials: KS
authors.lastname: Effrein
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, Georgia 30144.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: McMurry
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Ackley
authors.affiliation: Division of Biological Sciences, University of California San Diego, La Jolla, California 92093.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Chisholm
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, Georgia 30144 mhudso28@kennesaw.edu.
authors.forename: Martin L
authors.identifier: http://orcid.org/0000-0002-2628-035X
authors.initials: ML
authors.lastname: Hudson
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D036342:Ephrins / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D055879:Gene Knock-In Techniques; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D007395:Interneurons / Q000378:metabolism; D008954:Models, Biological; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D036081:Receptors, Eph Family / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; C470369:EFN-4 protein, C elegans; D036342:Ephrins; D019812:Heparan Sulfate Proteoglycans; D036081:Receptors, Eph Family
keywords: Eph receptor; axon branching; axon outgrowth; ephrin; heparan sulfate proteoglycan