Three mammalian fringe family members, Manic, Radical and Lunatic Fringe, have been identified as proteins related to Drosophila fringe, a protein involved in development. Fringe proteins act upstream of the Notch signaling pathway and are involved in boundary determination during segmentation. Each mammalian fringe displays different patterns of expression, though all are expressed in the mouse embryo as well as in many adult tissues. Radical fringe plays a key role in the development of the limb bud. Lunatic fringe is required for normal somite segmentation and patterning and is thought to be a target of the molecular clock. Manic fringe, also involved in somatic development, has been shown to render mouse NIH/3T3 cells tumorigenic in SCID mice.