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

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 GM1 may be enriched in granule cell growth cones and play an important role in neurite outgrowth. A striking accumulation of GM1, which may result from altered metabolism, occurred in the adult wv/wv mice. GD3 was heavily concentrated in undifferentiated granule cells, but was rapidly displaced by the more complex gangliosides during differentiation. GD1a became enriched in granule cells during formation of synaptic and dendritic membranes, whereas GT1a appeared enriched in Purkinje cell synaptic spines. A possible fucose-containing ganglioside was quantitated only in the wv/wv mice. Ganglioside GT1b became enriched in granule cells during synaptogenesis, whereas GQ1b became enriched in these cells after synaptogenesis. The concentrations of GT1b and especially GQ1b 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.