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 2 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 developmental 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(x) carbohydrate, and immunostaining patterns of embryonic brain sections by FORSE-1 and a known anti-Le(x) antibody are identical. Finally, purified FORSE-1 specifically recognizes Le(x)-containing glycoconjugates in ELISAs. The pattern of FORSE-1 labeling, the identification of its epitope as Le(x), which has been implicated in cell adhesion, and the presence of Le(x) on phosphacan suggest that this carbohydrate epitope may play a role in adhesive interactions important for proliferation, cell migration, or axon guidance.