GENETIC AND MOLECULAR CHARACTERIZATION OF A NOTCH MUTATION IN ITS DELTA-BINDING AND SERRATE-BINDING DOMAIN IN DROSOPHILA

The Drosophila Notch gene product is a transmembrane protein that func tions as a receptor of intercellular signals in several Drosophila dev elopmental processes. Two other transmembrane proteins, encoded by the genes Delta and Serrate, genetically and molecularly behave as Notch ligands. All these proteins share the presence of epidermal growth fac tor (EGF)-like repeats in their extracellular domain. The Notch protei n has 36 EGF-like repeats, 2 of which, numbers 11 and 12, are required for the interaction with the Delta and Serrate ligands. We have isola ted and molecularly characterized a Notch mutation in its Delta- and S errate-binding domain that behaves genetically as both a Notch antimor phic and a loss-of-function mutation. This mutation, N(M1), carries a Glu --> Val substitution in the Notch EGF repeat 12. The N(M1) allele interacts with other Notch alleles such as Abruptex and split and with mutations in the Notch-ligand genes Delta and Serrate. The basis for the genetic antimorphism of N(M1) seems to reside in the titration of Notch wild-type products into N(M1)/N+ nonfunctional dimers and/or the titration of Delta products into nonfunctional ligand-receptor comple xes.