A Chick Homologue ofSerrateand Its Relationship withNotchandDeltaHomologues during Central Neurogenesis

AbstractIn theDrosophilanervous system, lateral inhibition regulates commitment to a neural fate by preventing neighbouring cells from developing alike. This signalling process is mediated by two transmembrane proteins—Notch as receptor and Delta as its ligand. The Delta-related protein Serrate also acts as a Notch ligand inDrosophila,but in a different developmental process that organises patterning of the wing. We have previously shown that lateral inhibition operates at early stages of neurogenesis in vertebrates, via genes homologous toDrosophila DeltaandNotch.We report here the cloning of a chickSerratehomologue,C-Serrate-1.This gene is expressed in the central nervous system, as well as in the cranial placodes, nephric epithelium, vascular system, and distal limb-bud mesenchyme. In most of these sites, its expression is associated with expression ofC-Notch-1andC-Delta-1.All three genes are expressed in the ventricular zone of the hindbrain and spinal cord, throughout the period when neurons are being born. Within this zone,C-Delta-1andC-Serrate-1are expressed in complementary subsets of nondividing cells that appear to be nascent neurons:C-Serrate-1expression is restricted to specific locations along the dorsoventral axis, forming narrow bands extending from the anterior hindbrain to the tail. Our observations strongly suggest that Delta–Notch signalling delivers lateral inhibition not only early but throughout vertebrate neurogenesis to regulate neuronal commitment, and that Serrate–Notch signalling may act similarly in this process. By analogy with its role inDrosophilawing patterning,C-Serrate-1may also have a role in organising the dorso-ventral pattern of the neural tube. We argue that signalling via Notch maintains neurogenesis, both in vertebrates and in flies, by keeping a proportion of the neuroepithelial cells in an uncommitted stem-cell-like state