title: gdnf activates midline repulsion by Semaphorin3B via NCAM during commissural axon guidance.
abstract: The Neurotrophic factor gdnf plays diverse developmental roles, supporting survival and also acting as a chemoattractant for axon and cell migration. We report that in the developing spinal cord, a focal source of gdnf is present in the floor plate (FP) where commissural axons cross the midline. Gdnf has no direct guidance properties but switches on the responsiveness of crossing commissural growth cones to the midline repellent Semaphorin3B by suppressing calpain-mediated processing of the Sema3B signaling coreceptor Plexin-A1. Analysis of single and double mutant mouse models indicates that although gdnf is the principal trigger of Sema3B midline repulsion, it acts with another FP cue, NrCAM. Finally, genetic and in vitro experiments provide evidence that this gdnf effect is RET independent and mediated by NCAM/GFRα1 signaling. This study identifies a regulator of midline crossing and reveals interplays between Semaphorin and gdnf signaling during axon guidance.
authors.affiliation: University of Lyon, University Claude Bernard Lyon1, CGphiMC UMR CNRS 5534, 69622 Villeurbanne, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Charoy
authors.forename: Homaira
authors.initials: H
authors.lastname: Nawabi
authors.forename: Florie
authors.initials: F
authors.lastname: Reynaud
authors.forename: Edmund
authors.initials: E
authors.lastname: Derrington
authors.forename: Muriel
authors.initials: M
authors.lastname: Bozon
authors.forename: Kevin
authors.initials: K
authors.lastname: Wright
authors.forename: Julien
authors.initials: J
authors.lastname: Falk
authors.forename: Françoise
authors.initials: F
authors.lastname: Helmbacher
authors.forename: Karine
authors.initials: K
authors.lastname: Kindbeiter
authors.forename: Valérie
authors.initials: V
authors.lastname: Castellani
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D019521:Body Patterning / Q000235:genetics; D002154:Calpain / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D014162:Transfection
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C492114:Plxna1 protein, mouse; D011956:Receptors, Cell Surface; D039961:Semaphorins; D002154:Calpain