Roles of O-Fucose Glycans in Notch Signaling Revealed by Mutant Mice

Notch receptor signaling is important for many developmental processes in the metazoa. Insights into how Notch receptor signaling is regulated have been obtained from the characterization of mutants of model organisms in which Notch signaling is perturbed. Here we describe the effects of mutations that alter the glycosylation of Notch receptors and Notch ligands in the mouse. The extracellular domain of Notch receptors and Notch ligands carries N-glycans and O-glycans, including O-fucose and O-glucose glycans. Mutations in several genes that inhibit the synthesis of O-fucose glycans, and one that also affects the maturation of N-glycans, cause Notch signaling defects and disrupt development.