We have found, with chemical and immunological methods, a series of complex glycolipids in fetal brain that are stage specific i.e. change in concentration during development. These include glycolipids that express the SSEA-1 (Le(x), 7A), HNK-1 (4F4), WCC4, 7C7 (GD3, LD1), Lewis a and SSEA-3 determinants. Definitive structure characterization of all of the complex glycolipids detected in fetal brain is needed to provide a firm foundation for future developmental and functional studies. The expression of cell-surface glycolipid structures may be primarily regulated by specific biosynthetic steps and changes in glycosyltransferase activities are probably critical events in developmental processes. Changes in glycolipid levels should correlate with changes in the activities of transferases that are rete-limiting steps in the biosynthesis.
The specific aims are: 1) To continue studies on the isolation and chemical characterization of complex neutral glycosphingolipids from human fucosidosis and GM1 gangliosidosis, as well as, fetal bovine and porcine brain. 2) To study the expression and regulation of these glycolipids in rodent brains during development by HPLC, immunoblotting and LC/MS techniques. Such data will complement the immunohistochemical data already obtained with antibodies to the SSEA-1, WCC4 and 4F4 antigens. 3) To characterize and determine the activities of specific glycosyltransferases which are likely to be rate-limiting steps in the synthesis of SSEA-1 glycolipid antigens. These studies should provide fundamental information relevant to our central hypothesis that specific developmentally regulated carbohydrate structures, interacting with cell surface or extracellular receptors, are involved in cellular differentiation and growth regulation during nervous system development.
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