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 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.

Substrate reduction reduces gangliosides in postnatal cerebrum-brainstem and cerebellum in GM1 gangliosidosis mice

“…In contrast to the C-BS, where GM1 is a major ganglioside, GM1 was a minor ganglioside in the cerebellum of normal B6 mice at p-15 (Table 2). This is consistent with previous observations in normal mice (29,47). However, GM1 was ‫-4ف‬fold greater in the C-BS and ‫-5ف‬ fold greater in the cerebellum of the untreated ␤-gal Ϫ/Ϫ mice than in the untreated B6 mice (Table 2).…”

“…GD3 is enriched in vertebrate CNS neuroectodermal cells, including granule cells of the EGL, in the developing mouse cerebellum (29,(47)(48)(49)(50)(51)(52)(53). Our findings indicate that inhibition of total ganglioside and GD3 biosynthesis did not affect the migration of granule cells from the EGL to the internal granular layer.…”

Expression of GD3 ganglioside by developing rat cerebellar purkinje cells in situ

“…Studies using mouse neurological mutants have suggested that G D~ is concentrated in undifferentiated granule cell neurons of the cerebellum and also in reactive astrocytes [Seyfried et al, 1983. Immunocytochemical studies using two different monoclonal antibodies against GD3 have confirmed and extended these biochemical studies [Goldman et al, 1984;Curtis et al, 19881.…”

Inhibition of Glycosphingolipid Biosynthesis Does Not Impair Growth or Morphogenesis of the Postimplantation Mouse Embryo

“…A significant body of literature suggests that gangliosides are expressed in the CNS in a cellspecific and developmentally regulated fashion (Ledeen, 1985;Yu, 1993). Furthermore, changes in GSL expression during development correlate with changes in cellular growth and migration, differentiation, neuritogenesis, and synaptogenesis (Suzuki, 1965;Irwin et al, 1980;Seyfried et al, 1983;Bremer et al, 1986;Fenderson et al, 1987;Andrews et al, 1990;Hakomori, 1990;Schengrund, 1990;Rosenberg et al, 1992;Rosenberg and Noble, 1993;Wu et al, 1995;Zeng et al, 1995). These findings, together with evidence for a phylogenetic conservation of ganglioside expression and the absence of natural ganglioside biosynthetic mutations, have led to the hypothesis that GSLs play a critical role in developmental processes (Seyfried, 1988;Irvine and Seyfried, 1994).…”