Fringe differentially modulates Jagged1 and Delta1 signalling through Notch1 and Notch2

Proteins encoded by the fringe family of genes are required to modulate Not ch signalling in a wide range of developmental contexts. Using a cell co-cu lture assay, we find that mammalian Lunatic fringe (Lfng) inhibits Jagged1- mediated signalling and potentiates Delta1-mediated signalling through Notc h1. Lfng localizes to the Golgi, and Lfng-dependent modulation of Notch sig nalling requires both expression of Lfng in the Notch-responsive cell and t he Notch extracellular domain. Lfng does not prevent binding of soluble Jag ged1 or Delta1 to Notch1-expressing cells. Lfng potentiates both Jagged1- a nd Delta1-mediated signalling via Notch2, in contrast to its actions with N otch1. Our data suggest that Fringe-dependent differential modulation of th e interaction of Delta/Serrate/Lag2 (DSL) ligands with their Notch receptor s is likely to have a significant role in the combinatorial repertoire of N otch signalling in mammals.