Cellular localization of gangliosides in the developing mouse cerebellum: analysis using the weaver mutant

Abstract: The distribution of gangliosides was studied in the weaver ( wv/wv ) mutant mouse, where the vast majority of postmitotic granule cell neurons die prior to their differentiation. The wv mutation also shows a dosage effect, as granule cell migration is slowed or retarded in the + /wv heterozygotes. By correlating changes in ganglioside composition with the well-documented histological events that occur during cerebellar development in the normal (+/+), heterozygous ( +/wv ), and weaver ( wv/ wv ) mutant mice, information was obtained on the cellular localization and function of gangliosides. Ganglioside G_M1 may be enriched in granule cell growth cones and play an important role in neurite outgrowth. A striking accumulation of G_M1, which may result from altered metabolism, occurred in the adult wvlwv mice. G_D3 was heavily concentrated in undifferentiated granule cells, but was rapidly displaced by the more complex gangliosides during differentiation. G_D1a became enriched in granule cells during formation of synaptic and dendritic membranes, whereas G_T1a appeared enriched in Purkinje cell synaptic spines. A possible fucose-containing ganglioside was quantitated only in the wvlwv mice. Ganglioside G_T1b became enriched in granule cells during synaptogenesis, whereas G_Q1b became enriched in these cells after synaptogenesis. The concentrations of G_T1b and especially G_Q1b increased continuously with age. Our results provide further evidence for a differential cellular enrichment of gangliosides in the mouse cerebellum and also suggest that certain gangliosides may be differentially distributed within the membranes of these cells at various stages of development.