Intraretinal pathfinding of ganglion cell axons is perturbed by a monoclonal antibody specific for a G4/Ng-CAM-like cell adhesion molecule.
To identify molecular components involved in directed axonal outgrowth and in neural pattern formation, hybridoma technology was employed using the visual system of the chicken as a model system. Using cell surface protein fractions as immunogens, we obtained the monoclonal antibody mAb C4, which binds to a 135 kDa cell surface glycoprotein of the high-mannose or complex type. Within the retina, the C4 antigen is found exclusively in the optic fiber layer. Immuno-double labeling of retinal whole mounts with a glial marker and mAb C4 suggests that the C4 antigen is restricted to ganglion cell axons but not found on Müller glial endfeet. Biochemical and histological data reveal similarities between the C4-antigen and G4/NgCAM. Addition of mAb C4 to retina explants cultured on a striped carpet of tectal cell membranes leads to defasciculation of outgrowing axons, suggesting that the C4 antigen serves as an axon cell adhesion molecule (Ax-CAM). Axon elongation on neighboring axons can be also inhibited by the application of mAb C4 to embryonic retina whole mounts in vitro. The aberrant axon growth into incorrect retina layers observed under these conditions suggests that the C4 antigen functions as a guiding cue for the generation of the retinal optic fiber layer.
Schlosshauer
B
B
Max-Planck Institut für Entwicklungsbiologie, Tübingen, F.R.G.
Dütting
D
D
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity / Q000276:immunology; D001369:Axons / Q000648:ultrastructure*; D015816:Cell Adhesion Molecules, Neuronal / Q000276:immunology*; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D005455:Fluorescent Antibody Technique; D009474:Neurons / Q000648:ultrastructure*; D012160:Retina / Q000648:ultrastructure*
D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal