FORSE-1, AN ANTIBODY THAT LABELS REGIONALLY RESTRICTED SUBPOPULATIONSOF 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 subpopulat ions of progenitor cells give rise to different adult brain structures . The labeling pattern of the FORSE-1 antibody subdivides the neuroepi thelium of the embryonic forebrain into domains resembling those of ce rtain transcription factors, suggesting that the FORSE-1 epitope may b e involved in the specification of developmental compartments. Therefo re, it is important to determine the identity of the antigen(s) recogn ized by FORSE-1. On immunoblots, FORSE-1 recognizes a single, high-mol ecular-weight species, which we have identified as phosphacan, a brain -specific chondroitin sulfate proteoglycan that binds neural cell adhe sion molecules. This identification is based on cross-immunoprecipitat ions and immunoblotting using an anti-phosphacan antibody and FORSE-1. FORSE-1 also recognizes two major neutral glycolipids in embryonic br ain. The FORSE-1 epitope is sensitive to endo-beta-galactosidase, sugg esting that the epitope corresponds to a carbohydrate moiety. Moreover , immunoprecipitates of the proteoglycan bearing the FORSE-1 epitope b ind antibodies that recognize the Le(x) carbohydrate, and immunostaini ng patterns of embryonic brain sections by FORSE-1 and a known anti-Le (x) antibody are identical. Finally, purified FORSE-1 specifically rec ognizes Le(x)-containing glycoconjugates in ELISAs. The pattern of FOR SE-1 labeling, the identification of its epitope as Le(x), which has b een implicated in cell adhesion, and the presence of Le(x) on phosphac an suggest that this carbohydrate epitope may play a role in adhesive interactions important for proliferation, cell migration, or axon guid ance.