title: Extracellular Engrailed participates in the topographic guidance of retinal axons in vivo.
abstract: Engrailed transcription factors regulate the expression of guidance cues that pattern retinal axon terminals in the dorsal midbrain. They also act directly to guide axon growth in vitro. We show here that an extracellular En gradient exists in the tectum along the anterior-posterior axis. Neutralizing extracellular Engrailed in vivo with antibodies expressed in the tectum causes temporal axons to map aberrantly to the posterior tectum in chick and Xenopus. Furthermore, posterior membranes from wild-type tecta incubated with anti-Engrailed antibodies or posterior membranes from Engrailed-1 knockout mice exhibit diminished repulsive activity for temporal axons. Since EphrinAs play a major role in anterior-posterior mapping, we tested whether Engrailed cooperates with EphrinA5 in vitro. We find that Engrailed restores full repulsion to axons given subthreshold doses of EphrinA5. Collectively, our results indicate that extracellular Engrailed contributes to retinotectal mapping in vivo by modulating the sensitivity of growth cones to EphrinA.
authors.affiliation: Institute of Developmental Genetic, Helmhotz Zentrum Munich, Ingolstädter Landstrasse 1, 89675 Neuherberg, Germany; MPI of Psychiatry, Kraepelinstasse 1-10, 8004 Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wizenmann
authors.affiliation: Group "Development and Neuropharmacology" (Equipe FRM), UMR 8542 CNRSENS-CDF, Collège de France, 11 place M. Berthelot, 75231 Paris, Cedex 05, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brunet
authors.affiliation: Department of Physiology, Development and Neurosciences, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
authors.forename: Joyce
authors.initials: J
authors.lastname: Lam
authors.affiliation: Group "Development and Neuropharmacology" (Equipe FRM), UMR 8542 CNRSENS-CDF, Collège de France, 11 place M. Berthelot, 75231 Paris, Cedex 05, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Sonnier
authors.affiliation: Group "Development and Neuropharmacology" (Equipe FRM), UMR 8542 CNRSENS-CDF, Collège de France, 11 place M. Berthelot, 75231 Paris, Cedex 05, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Beurdeley
authors.affiliation: Institute of Developmental Genetic, Helmhotz Zentrum Munich, Ingolstädter Landstrasse 1, 89675 Neuherberg, Germany; MPI of Psychiatry, Kraepelinstasse 1-10, 8004 Munich, Germany.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Zarbalis
authors.affiliation: Institute of Developmental Genetic, Helmhotz Zentrum Munich, Ingolstädter Landstrasse 1, 89675 Neuherberg, Germany; MPI of Psychiatry, Kraepelinstasse 1-10, 8004 Munich, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Weisenhorn-Vogt
authors.affiliation: Department of Physiology, Development and Neurosciences, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Weinl
authors.affiliation: Department of Physiology, Development and Neurosciences, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
authors.forename: Asha
authors.initials: A
authors.lastname: Dwivedy
authors.affiliation: Group "Cell Biology of Homeoproteins", UMR 8542 CNRS-ENS-CDF, Collège de France, 11 place M. Berthelot, 75231 Paris, Cedex 05, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Joliot
authors.affiliation: Institute of Developmental Genetic, Helmhotz Zentrum Munich, Ingolstädter Landstrasse 1, 89675 Neuherberg, Germany; MPI of Psychiatry, Kraepelinstasse 1-10, 8004 Munich, Germany.|Department of Developmental Genetics, Technical University, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.affiliation: Department of Physiology, Development and Neurosciences, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Holt
authors.affiliation: Group "Development and Neuropharmacology" (Equipe FRM), UMR 8542 CNRSENS-CDF, Collège de France, 11 place M. Berthelot, 75231 Paris, Cedex 05, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Prochiantz
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002633:Chemotaxis / Q000502:physiology*; D002642:Chick Embryo; D005110:Extracellular Space / Q000378:metabolism*; D020439:Growth Cones / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D036081:Receptors, Eph Family / Q000378:metabolism; D012160:Retina / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology; D013477:Superior Colliculi / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D014795:Visual Pathways / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D014981:Xenopus
chemical_list: C080330:En1 protein, mouse; D018398:Homeodomain Proteins; D036081:Receptors, Eph Family