The formation of boundaries between groups of cells is a universal feature of metazoan development. Drosophila fringe modulates the activation of the Notch signal transduction pathway at the dorsal-ventral boundary of the wing imaginal disc. Three mammalian fringe-related family members have been cloned and characterized: Manic, Radical and Lunatic Fringe. Expression studies in mouse embryos support a conserved role for mammalian Fringe family members in participation in the Notch signaling pathway leading to boundary determination during segmentation. In mammalian cells, Drosophila fringe and the mouse Fringe proteins are subject to posttranslational regulation at the levels of differential secretion and proteolytic processing. When misexpressed in the developing Drosophila wing imaginal disc the mouse Fringe genes exhibit conserved and differential effects on boundary determination.