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Cellular Distribution of Gangliosides in the Developing Mouse Cerebellum: Analysis Using the Staggerer Mutant
Author(s) -
Seyfried Thomas N.,
Bernard David J.,
Yu Robert K.
Publication year - 1984
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1984.tb12856.x
Subject(s) - mutant , cerebellum , neuroscience , biology , distribution (mathematics) , ganglioside , chemistry , microbiology and biotechnology , biochemistry , mathematics , gene , mathematical analysis
The distribution of cerebellar gangliosides was studied in staggerer ( sg/sg ) mutant mice, where the majority of granule cells die after completing their migration across the molecular layer. In addition, the external granule cell layer in ( sg/sg ) mice persists longer than in normal mice. Moreover, in the sg/sg cerebellum, Purkinje cells are significantly reduced in number, and almost none have tertiary branchlet spines. The loss of Purkinje cells and granule cells in sg/sg mice is accompanied by an early‐onset reactive gliosis that continues through adulthood. By correlating changes in ganglioside composition with the well‐documented histological events of cerebellar development in normal and sg/sg mice, we obtained strong evidence for a nonrandom cellular distribution of gangliosides. The sharpest reduction in the G D1a content of sg/sg cerebellum occurred after 15 days of age, coincident with granule cell loss. G T1a , on the other hand, was significantly reduced from 15 through 150 days in the sg/sg mice. G D3 is a major ganglioside of the undifferentiated granule cell, but it becomes rapidly displaced by the more complex gangliosides with the onset of granule cell maturation. In the sg/sg mice, G D3 persisted at abnormally high levels from 15 to 28 days and then accumulated through adulthood. These findings, and those from other cerebellar mouse mutants, suggest that G D1a is enriched in granule cells and that G T1a is enriched in Purkinje cells. Our findings also suggest that G T1a is more concentrated in branchlet spines than in other regions of the Purkinje cell membrane. G T1b appears to be enriched in both granule cells and Purkinje cells, whereas G M1 appears to be enriched in myelin. Furthermore, the apparent persistence of the embryonic ganglioside G D3 in sg/sg mice results from an early‐onset reactive gliosis, together with a partial retardation in granule cell maturation. The accumulation of G D3 beyond 28 days reflects the continued accretion of G D3 in reactive glia.