REGULATION OF GLOBOPENTOSYLCERAMIDE EXPRESSION

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DESCRIPTION (Adapted from Applicant's Description): Glycolipids are cell surface molecules which consist of distinct carbohydrate structures attached to a ceramide backbone. Considerable evidence suggests that these molecules play a role in tissue development and cellular differentiation. However, the precise role of glycolipids in cellular and developmental biology is unknown. Moreover, factors which regulate glycolipid expression during development have not been elucidated. The studies in this proposal address the developmental regulation of globopentosylceramide (GbO5) expression. This glycolipid is expressed at specific times during the development of mouse placenta, testis, and ovaries, and has been suggested to play a role in their development. Additionally, this glycolipid is a marker for the state of differentiation of some cell types in adult mice. In order to study the developmental regulation of GbO5 expression and the role of this glycolipid in differentiation, the enzyme GbO5 synthetase (N-acetylgalactosaminyltransferase) will be purified and its amino acid sequence will be determined. The gene encoding GbO5 synthetase will be isolated and cloned. The temporal and spatial regulation of Gb05 gene expression during murine development will then be investigated and corroborated with immunohistochemical studies. Future studies will be investigated by the results of manipulating GbO5 expression in cultured cell lines, and eventually in a transgenic mouse model. GbO5 expression may serve as a model for the regulation and function of glycolipid expression in general. Thus, the studies outlined in this proposal may enhance our understanding of the role that glycolipids play in development and differentiation.