The embryonic expression of the Notch locus of Drosophila melanogaster and the implications of point mutations in the extracellular EGF-like domain of the predicted protein.

The Notch locus of Drosophila melanogaster is one of a small number of zygotically acting 'neurogenic' genes necessary for the correct segregation of neural from epidermal lineages during embryogenesis. The predicted gene product is implicated in a cell interaction mechanism required to achieve this ectodermal differentiation. We have examined wild-type Notch expression by in situ hybridization and find it to be expressed in more cells than we would have predicted given a sole function in regulating neurogenesis. We conclude from these data that Notch plays a more general role in development. In order to assess the dependence of Notch expression on other neurogenic gene function we have hybridized Notch probes to Enhancer of split mutants which are known to interfere with expression of Notch phenotypes. We intimate that the nature of interaction between these genes is not at the level of transcription. Instead, the DNA sequence of split, which is a missense mutation in the EGF-like extracellular domain of the Notch protein, suggests a direct biochemical interaction between Notch and E(spl) proteins. The similar site of a second point mutation, AxE2, implies that protein interactions also occur between Notch proteins. Finally we discuss the general implications of our findings with a view to the models and mechanisms of Notch action in regulating individual cellular interactions during development.