Glycosylation of specific Notch EGF repeats by Ofut1 and Fringe regulates Notch signaling in Drosophila

We have reported important roles in Drosophila Notch signaling for GlcNAc-fucose-O glycans on three sites: EGF8, 9 and 12. O-fucose monosaccharide on EGF12 (in the absence of Fringe) is essential for Delta-mediated lateral inhibition in embryos. However, wing vein development depends on addition of GlcNAc to EGF8 and 12 by Fringe, with minor contribution from EGF9. Fringe modifications of EGF8 and 12 together prevent Notch from cis-inhibiting Serrate, thereby promoting normal wing margin formation. Our work shows the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions.