Extracellular Engrailed participates in the topographic guidance of retinal axons in vivo.
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.
Wizenmann
Andrea
A
Institute of Developmental Genetic, Helmhotz Zentrum Munich, Ingolstädter Landstrasse 1, 89675 Neuherberg, Germany; MPI of Psychiatry, Kraepelinstasse 1-10, 8004 Munich, Germany.
Brunet
Isabelle
I
Group "Development and Neuropharmacology" (Equipe FRM), UMR 8542 CNRSENS-CDF, Collège de France, 11 place M. Berthelot, 75231 Paris, Cedex 05, France.
Lam
Joyce
J
Department of Physiology, Development and Neurosciences, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Sonnier
Laure
L
Group "Development and Neuropharmacology" (Equipe FRM), UMR 8542 CNRSENS-CDF, Collège de France, 11 place M. Berthelot, 75231 Paris, Cedex 05, France.
Beurdeley
Marine
M
Group "Development and Neuropharmacology" (Equipe FRM), UMR 8542 CNRSENS-CDF, Collège de France, 11 place M. Berthelot, 75231 Paris, Cedex 05, France.
Zarbalis
Konstantinos
K
Institute of Developmental Genetic, Helmhotz Zentrum Munich, Ingolstädter Landstrasse 1, 89675 Neuherberg, Germany; MPI of Psychiatry, Kraepelinstasse 1-10, 8004 Munich, Germany.
Weisenhorn-Vogt
Daniela
D
Institute of Developmental Genetic, Helmhotz Zentrum Munich, Ingolstädter Landstrasse 1, 89675 Neuherberg, Germany; MPI of Psychiatry, Kraepelinstasse 1-10, 8004 Munich, Germany.
Weinl
Christine
C
Department of Physiology, Development and Neurosciences, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Dwivedy
Asha
A
Department of Physiology, Development and Neurosciences, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Joliot
Alain
A
Group "Cell Biology of Homeoproteins", UMR 8542 CNRS-ENS-CDF, Collège de France, 11 place M. Berthelot, 75231 Paris, Cedex 05, France.
Wurst
Wolfgang
W
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.
Holt
Christine
C
Department of Physiology, Development and Neurosciences, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Prochiantz
Alain
A
Group "Development and Neuropharmacology" (Equipe FRM), UMR 8542 CNRSENS-CDF, Collège de France, 11 place M. Berthelot, 75231 Paris, Cedex 05, France.
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
C080330:En1 protein, mouse; D018398:Homeodomain Proteins; D036081:Receptors, Eph Family