Inhibition of glycosphingolipid biosynthesis does not impair growth or morphogenesis of the postimplantation mouse embryo

John V. Brigande, Frances M. Platt, Thomas N. Seyfried

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Whole embryo culture (WEC) of organogenesis-stage mouse embryos was adapted for glycosphingolipid (GSL) metabolic studies to evaluate the hypothesis that de novo GSL biosynthesis is a prerequisite for growth and morphogenesis of the early postimplantation embryo. WEC supports the growth and development of postimplantation mouse embryos to stages that are indistinguishable from those achieved in vivo. N- Butyldeoxygalactonojirimycin (NB-DGJ) is an N-alkylated imino sugar that specifically inhibits biosynthesis of all glucosylceramide-based GSLs. NB- DGJ inhibited glucosylceramide and lactosylceramide biosynthesis nearly completely and inhibited ganglioside biosynthesis ~90% in both the embryo and visceral yolk sac. NB-DGJ also significantly reduced total ganglioside content in both the embryo and visceral yolk sac as estimated by the cholera toxin immunooverlay technique. A shift in expression from the structurally simple to the structurally complex gangliosides was also observed in NB-DGJ- treated embryos and yolk sacs. Despite causing major changes in GSL biosynthesis and composition, NB-DGJ had no effect on embryo viability, growth, or morphology. The findings suggest that de novo GSL biosynthesis may not be a prerequisite for the growth and morphogenesis of the organogenesis- stage mouse embryo.

Original languageEnglish (US)
Pages (from-to)871-882
Number of pages12
JournalJournal of neurochemistry
Volume70
Issue number2
DOIs
StatePublished - Feb 1998

Keywords

  • GM1
  • Gangliosides
  • N-Butyldeoxygalactonojirimycin
  • Organogenesis
  • Whole embryo culture

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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