COMPLEX ASPARAGINE-LINKED OLIGOSACCHARIDES ARE REQUIRED FOR MORPHOGENIC EVENTS DURING POSTIMPLANTATION DEVELOPMENT

Complex asparagine (N)-linked oligosaccharides appear late in phylogen y and are highly regulated in vertebrates. Variations in these structu res are found on the majority of cell-surface and secreted proteins. C omplex N-linked oligosaccharide biosynthesis is initiated in the Golgi apparatus by the action of Mgat-1-encoded UDP-N-acetylglucosamine: al pha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GlcNAc-T I). To determine if these structures govern ontogenic processes in mam mals, mouse embryos were generated that lacked a functional Mgat-1 gen e, Inactivation of both Mgat-1 alleles produced deficiencies in GlcNAc -TI activity and complex N-linked oligosaccharides. Embryonic lethalit y occurred by day 10.5, thus establishing that complex N-linked oligos accharides are required during post-implantation development. Remarkab ly, embryonic development proceeded into day 9 with the differentiatio n of multiple cell types. Complex N-linked oligosaccharides are import ant for morphogenic processes as neural tube formation, vascularizatio n and the determination of left-right body plan asymmetry were impaire d in the absence of a functional Mgat-1 gene.