Complex asparagine-linked oligosaccharides are required for morphogenic events during post-implantation development.
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.
Metzler
M
M
Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Gertz
A
A
Sarkar
M
M
Schachter
H
H
Schrader
J W
JW
Marth
J D
JD
D000818:Animals; D001216:Asparagine / Q000378:metabolism*; D001483:Base Sequence; D002240:Carbohydrate Sequence; D004247:DNA; D004622:Embryo, Mammalian / Q000098:blood supply / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D005804:Genes, Lethal; D006410:Hematopoiesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D016296:Mutagenesis; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics; D009436:Neural Tube Defects / Q000235:genetics; D009844:Oligosaccharides / Q000378:metabolism*; D010641:Phenotype; D011247:Pregnancy; D013234:Stem Cells / Q000378:metabolism
D009844:Oligosaccharides; D001216:Asparagine; D004247:DNA; D017351:N-Acetylglucosaminyltransferases; C024850:alpha-1,3-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase I