title: Mechanisms of ephrin receptor protein kinase-independent signaling in amphid axon guidance in Caenorhabditis elegans.
abstract: Eph receptors and their ephrin ligands are key conserved regulators of axon guidance and can function in a variety of signaling modes. Here we analyze the genetic and cellular requirements for Eph signaling in a Caenorhabditis elegans axon guidance choice point, the ventral guidance of axons in the amphid commissure. The C. elegans Eph receptor EFN-1 has both kinase-dependent and kinase-independent roles in amphid ventral guidance. Of the four C. elegans ephrins, we find that only EFN-1 has a major role in amphid axon ventral guidance, and signals in both a receptor kinase-dependent and kinase-independent manner. Analysis of EFN-1 and EFN-1 expression and tissue-specific requirements is consistent with a model in which VAB-1 acts in amphid neurons, interacting with EFN-1 expressed on surrounding cells. Unexpectedly, left-hand neurons are more strongly affected than right-hand neurons by loss of Eph signaling, indicating a previously undetected left-right asymmetry in the requirement for Eph signaling. By screening candidate genes involved in Eph signaling, we find that the Eph kinase-independent pathway involves the ABL-1 nonreceptor tyrosine kinase and possibly the phosphatidylinositol 3-kinase pathway. Overexpression of ABL-1 is sufficient to rescue EFN-1 ventral guidance defects cell autonomously. Our results reveal new aspects of Eph signaling in a single axon guidance decision in vivo.
authors: Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California 92093.
authors: Emily N
authors: EN
authors: Grossman
authors: Claudiu A
authors: CA
authors: Giurumescu
authors: Andrew D
authors: AD
authors: Chisholm
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D036342:Ephrins / Q000235:genetics / Q000378:metabolism*; D017238:Genes, Helminth; D008954:Models, Biological; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D036081:Receptors, Eph Family / Q000235:genetics / Q000378:metabolism*; D012679:Sense Organs / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D036342:Ephrins; C403283:vab-2 protein, C elegans; D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; D036081:Receptors, Eph Family; C111040:vab-1 protein, C elegans; C516680:ABL-1 protein, C elegans; D016315:Proto-Oncogene Proteins c-abl
keywords: Abl tyrosine kinase; Ephrin; amphid; left–right asymmetry; phosphatidylinositol 3-kinase
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