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J Biol Chem, Vol. 273, Issue 31, 19634-19638, July 31, 1998
From the Section on Biochemical Genetics, Genetics and Biochemistry
Branch, NIDDK, National Institutes of Health,
Bethesda, Maryland 20892
The dramatic changes in the expression of GD3 and
other b-series gangliosides during neuronal development and
morphogenesis have led to a widely held belief that these gangliosides
may be necessary for neuronal differentiation. To determine directly if
GD3 and b-series gangliosides are required for neuronal
differentiation, we have produced embryonic stem (ES) cells with both
alleles of the GD3 synthase gene (GD3S) disrupted by
successive rounds of gene targeting. The double-targeted ES cells were
deficient in GD3 synthase activity and did not synthesize b-series
gangliosides. Despite this deficit, the GD3S(
Embryonic Stem Cells with a Disrupted GD3 Synthase Gene Undergo
Neuronal Differentiation in the Absence of b-Series Gangliosides
/
) ES
cells could be induced to undergo neuronal differentiation. Neuronally
differentiated wild-type and GD3S(
/
) ES cells formed a
complex neurite network around the embryoid bodies. Both types of
neuronal cells expressed the axon-specific cytoskeletal proteins,
neurofilament-M, and growth-associated protein-43 as well as the
dendrite-specific marker, microtubule-associated protein-2. Our results
indicate that GD3 synthase and b-series gangliosides are not necessary for the neuronal differentiation of uncommitted precursor cells.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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