Functional analysis of carbohydrate chains involved in the differentiation and migration of cerbellar granule cells.

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The aim of the project was to analyze the functions of gangliosides specifically expressed in cerebellar granule cells. We have obtained a number of significant findings as follows : (1) the expression of each ganglioside changed dramatically during the development of rat cerebellum, suggesting that specific gangliosides may play an imprtant role in regulating the early events responsible for orderly formation of cerebellar cortex ; (2) the expression of gangliosides in primary rat cerebellar cultures was also specific by using an immunohistochemical technique with monoclonal antibodies specific for gangliosides. These results suggested that several gangliosides may be useful markers for identifyiong cells in primary cultures of the rat cerebellum ; particularly b-series gangliosides such as GD2 and GD1b for the granule cells and O-Ac-LD1 for Purkinje cells ; (3) we isolated a cDNA clone encoded an O-Ac-disialoganglioside synthase by using a direct expression cloning from a rat cDNA library. The deduced amino acid sequence of the product was similar to the milk fat grobule membrane glycoprotein. These evidence would be useful for the elucidation of the role of gangliosides in the central nervous system, in particular, the functions of gangliosides expressed in the granule cells.