Structural requirements for Notch signalling with Delta and Serrate duringthe development and patterning of the wing disc of Drosophila

The Delta and Serrate proteins interact with the extracellular domain of th e Notch receptor and initiate signalling through the receptor. The two liga nds are very similar in structure and have been shown to be interchangeable experimentally; however, loss of function analysis indicates that they hav e different functions during development and analysis of their signalling d uring wing development indicates that the Fringe protein can discriminate b etween the two ligands. This raises the possibility that the signalling of Delta and Serrate through Notch requires different domains of the Notch pro tein. Here we have tested this possibility by examining the ability of Delt a and Serrate to interact and signal with Notch molecules in which differen t domains had been deleted. This analysis has shown that EGF-like repeats 1 1 and 12, the RAM-23 and cdc10/ankyrin repeats and the region C-terminal to the cdc10/ankyrin repeats of Notch are necessary for both Delta and Serrat e to signal via Notch. They also indicate, however, that Delta and Serrate utilise EGF-like repeats 24-26 of Notch for signalling, but there are signi ficant differences in the way they utilise these repeats.