Complex asparagine-linked oligosaccharides are required for morphogenic events during post-implantation development

EMBO J. 1994 May 1;13(9):2056-65.

Abstract

Complex asparagine (N)-linked oligosaccharides appear late in phylogeny and are highly regulated in vertebrates. Variations in these structures are found on the majority of cell-surface and secreted proteins. Complex N-linked oligosaccharide biosynthesis is initiated in the Golgi apparatus by the action of Mgat-1-encoded UDP-N-acetylglucosamine:alpha-3-D- mannoside beta-1,2-N-acetylglucosaminyltransferase I (GlcNAc-TI). To determine if these structures govern ontogenic processes in mammals, mouse embryos were generated that lacked a functional Mgat-1 gene. Inactivation of both Mgat-1 alleles produced deficiencies in GlcNAc-TI activity and complex N-linked oligosaccharides. Embryonic lethality occurred by day 10.5, thus establishing that complex N-linked oligosaccharides are required during post-implantation development. Remarkably, embryonic development proceeded into day 9 with the differentiation of multiple cell types. Complex N-linked oligosaccharides are important for morphogenic processes as neural tube formation, vascularization and the determination of left-right body plan asymmetry were impaired in the absence of a functional Mgat-1 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asparagine / metabolism*
  • Base Sequence
  • Carbohydrate Sequence
  • DNA
  • Embryo, Mammalian / blood supply
  • Embryo, Mammalian / metabolism
  • Embryonic Development* / genetics
  • Female
  • Fetal Growth Retardation / genetics
  • Genes, Lethal
  • Hematopoiesis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Morphogenesis / genetics
  • Morphogenesis / physiology*
  • Mutagenesis
  • N-Acetylglucosaminyltransferases / genetics
  • Neural Tube Defects / genetics
  • Oligosaccharides / metabolism*
  • Phenotype
  • Pregnancy
  • Stem Cells / metabolism

Substances

  • Oligosaccharides
  • Asparagine
  • DNA
  • N-Acetylglucosaminyltransferases
  • alpha-1,3-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase I