The enrichment of gangliosides in neuronal membranes suggests that they play an important role in CNS development. We recently found a marked tetrasialoganglioside deficiency in twl/twl mutant mouse embryos at embryonic day (E)-11. The recessive twl/twl mutants die at embryonic ages E-9 to E-18 from failed neural differentiation in the ventral portion of the neural tube. In the present study, we examined the composition and distribution of gangliosides in twl/twl mutant mouse embryos at E-12. The total ganglioside sialic acid concentration was significantly lower in the mutants than in normal (+/-) embryos. The mutants also expressed significant deficiencies of gangliosides in the "b" metabolic pathway (GD3, GD1b, GT1b, and GQ1b) and elevations in levels of gangliosides in the "a" metabolic pathway (GM3, GM2, GM1, and GD1a). These findings suggest that the mutants have a partial deficiency in the activity of a specific sialyltransferase in the b pathway. Regional ganglioside distribution was also studied in E-12 normal mouse embryos. The ganglioside composition in heads and bodies was similar to each other and to whole embryos. Total ganglioside concentration and the distribution of b pathway gangliosides were significantly higher in neural tube regions than in nonneural tube regions. These findings suggest that b pathway gangliosides accumulate in differentiating neural cells and that the deficiency of these gangliosides in the twl/twl mutants is closely associated with failed neural differentiation.

The composition of whole embryo gangliosides at embryonic day E-12 was compared among the C57BL/6 (B6) DBA/2 (D2), and C3H mouse strains. N-acetylneuraminic acid was the predominant sialic acid species in the E-12 embryos. N-glycolyneuraminic acid was either undetectable or present in only trace amounts. Whole embryo ganglioside sialic concentration was significantly lower in D2 embryos than in B6 or C3H embryos. GM3 and GD3 were the most abundant ganglioside species in each strain and comprised approximately 75% of the total distribution. The D2 embryos expressed an elevation of GD1a and a reduction of GQ1b relative to B6 and C3H. Also, the level of GM1 was significantly higher in the D2 embryos than in the B6 or C3H embryos. Since a reduction of β-galactosidase activity and an elevation of GM1 concentration in brain were previously reported in postnatal DBA mice, our results suggest that the elevated GM1 in D2 embryos may result from a reduced activity of GM1 β-galactosidase.