title: Loss-of-function analysis of EphA receptors in retinotectal mapping.
abstract: EphA tyrosine kinases are thought to act as topographically specific receptors in the well-characterized projection map from the retina to the tectum. Here, we describe a loss-of-function analysis of EphA receptors in retinotectal mapping. Expressing patches of a cytoplasmically truncated EphA3 receptor in chick retina caused temporal axons to have reduced responsiveness to posterior tectal repellent activity in vitro and to shift more posteriorly within the map in vivo. A gene disruption of mouse EphA5, replacing the intracellular domain with beta-galactosidase, reduced in vitro responsiveness of temporal axons to posterior target membranes. It also caused map abnormalities in vivo, with temporal axons shifted posteriorly and nasal axons anteriorly, but with the entire target still filled by retinal axons. The anterior shift of nasal axons was not accompanied by increased responsiveness to tectal repellent activity, in contrast to the comparable anterior shift in ephrin-A knock-outs, helping to resolve a previous ambiguity in interpreting the ephrin gene knock-outs. The results show the functional requirement for endogenous EphA receptors in retinotectal mapping, show that the receptor intracellular domain is required for a forward signaling response to topographic cues, and provide new evidence for a role of axon competition in topographic mapping.
authors.affiliation: Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Feldheim
authors.forename: Masaru
authors.initials: M
authors.lastname: Nakamoto
authors.forename: Miriam
authors.initials: M
authors.lastname: Osterfield
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Gale
authors.forename: Thomas M
authors.initials: TM
authors.lastname: DeChiara
authors.forename: Rajat
authors.initials: R
authors.lastname: Rohatgi
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: John G
authors.initials: JG
authors.lastname: Flanagan
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D002642:Chick Embryo; D018390:Gene Targeting; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D036121:Receptor, EphA3 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D036123:Receptor, EphA5 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D036081:Receptors, Eph Family / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D017384:Sequence Deletion; D013477:Superior Colliculi / Q000166:cytology / Q000378:metabolism*; D014795:Visual Pathways / Q000166:cytology / Q000378:metabolism*
chemical_list: D036121:Receptor, EphA3; D036123:Receptor, EphA5; D036081:Receptors, Eph Family