FORSE-1, an antibody that labels regionally restricted subpopulations of progenitor cells in the embryonic central nervous system, recognizes the Le(x) carbohydrate on a proteoglycan and two glycolipid antigens.
A key problem in nervous system development is how distinct subpopulations of progenitor cells give rise to different adult brain structures. The labeling pattern of the FORSE-1 antibody subdivides the neuroepithelium of the embryonic forebrain into domains resembling those of certain transcription factors, suggesting that the FORSE-1 epitope may be involved in the specification of development compartments. Therefore, it is important to determine the identity of the antigen(s) recognized by FORSE-1. On immunoblots, FORSE-1 recognizes a single, high-molecular-weight species, which we have identified as phosphacan, a brain-specific chondroitin sulfate proteoglycan that binds neural cell adhesion molecules. This identification is based on cross-immunoprecipitations and immunoblotting using an anti-phosphacan antibody and FORSE-1. FORSE-1 also recognizes two major neutral glycolipids in embryonic brain. The FORSE-1 epitope is sensitive to endo-beta-galactosidase, suggesting that the epitope corresponds to a carbohydrate moiety. Moreover, immunoprecipitates of the proteoglycan bearing the FORSE-1 epitope bind antibodies that recognize the Le* carbohydrate, and immunostaining patterns of embryonic brain sections by FORSE-1 and a known anti-Le* antibody are identical. Finally, purified FORSE-1 specifically recognizes Le*-containing glycoconjugates in ELISAs. The pattern of FORSE-1 labeling, the identification of its epitope as Le*, which has implicated in cell adhesion, and the presence of Le* on phosphacan suggest that this carbohydrate epitope may play a role in adhesive interactions important for proliferation, cell migration, or axon guidance.
Allendoerfer
K L
KL
Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Magnani
J L
JL
Patterson
P H
PH
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000276:immunology; D000954:Antigens, Surface; D001921:Brain / Q000196:embryology* / Q000254:growth & development*; D002241:Carbohydrates / Q000276:immunology*; D000939:Epitopes; D006001:Glycoconjugates / Q000276:immunology; D006017:Glycolipids / Q000276:immunology; D006026:Glycoside Hydrolases; D007983:Lewis Blood Group Antigens; D011509:Proteoglycans / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism*; D001616:beta-Galactosidase / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000941:Antigens; D000954:Antigens, Surface; D002241:Carbohydrates; D000939:Epitopes; D006001:Glycoconjugates; D006017:Glycolipids; D007983:Lewis Blood Group Antigens; D011509:Proteoglycans; C092260:antigen FORSE-1; D006026:Glycoside Hydrolases; C026093:keratan-sulfate endo-1,4-beta-galactosidase; D001616:beta-Galactosidase