Fringe: Defining borders by regulating the Notch pathway

The Notch pathway mediates cell-cell interaction in many developmental processes. Multiple proteins regulate the Notch pathway, among these are the products of the fringe genes. The first fringe gene was identified in Drosophila, where it is involved in the formation of the dorsal/ventral border of the wing disc. It has now been found to be crucial for determining the dorsal/ventral border of the Drosophila eye. In vertebrates, fringe genes play roles in the formation of the apical ectodermal ridge, the dorsal/ventral border in the limb bud, and in the development of somitic borders. The roles of fringe in the neural tube or the eyes of vertebrate embryos are not clear, although it is unlikely that these roles are evolutionarily related to those in the same tissues in Drosophila. Genetic evidences suggest that Fringe protein functions by modulating the Notch signaling pathway, perhaps through differential regulation of Notch activation by different ligands; however, the mechanism underlying Fringe function remains to be investigated.