Notch in vertebrates--molecular aspects of the signal.

Notch is a receptor consisting of a single path transmembrane protein which is essential for stem cell regulation in both vertebrates and invertebrates. We have investigated the function of Notch signaling and found that ligands of the Notch receptor (Delta and Serrate) sometimes act as receptor modulators in a cell autonomous manner; the balance of their activity as ligands explains satisfactorily 'lateral inhibition' as well as 'lateral specification'. This model explains not only fly morphogenesis, but also the general regulation of stem cells. In vertebrates, members of a novel family of genes which encode small secretory proteins, CCN, were demonstrated to bind to Notch and stimulate signaling. This is not a ligand type binding, but rather a modifier of the protein structure of Notch, so as to form a macromolecular complex. This association may open up novel perspectives on Notch signaling, for instance in the movement of cells involved in somite segmentation or angiogenesis. Thus, a well-conserved signal such as Notch seems to have changed in function during the evolution of vertebrates.