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The phenotypes and genetic interactions associated with mutations in the Drosophila mastermind (mam) gene have implicated it as a component of the Notch signaling pathway. However, its function and site of action within many tissues requiring Notch signaling have not been thoroughly investigated. To address these questions, we have constructed truncated versions of the Mam protein that elicit dominant phenotypes when expressed in imaginal tissues under GAL4-UAS regulation. By several criteria, these effects appear to phenocopy loss of function for the Notch pathway. When expressed in the notum, truncated Mam results in failure of lateral inhibition within proneural clusters and perturbations in cell fate specification within the sensory organ precursor cell lineage. Expression in the wing is associated with vein thickening and margin defects, including nicking and bristle loss. The truncation-associated wing margin phenotypes are modified by mutations in Notch and Wg pathway genes and are correlated with depressed expression of wg, cut, and vg. These data support the idea that Mam truncations have lost key effector domains and therefore behave as dominant-negative proteins. Coexpression of Delta or an activated form of Notch suppresses the effects of the Mam truncation, suggesting that Mam can function upstream of ligand-receptor interaction in the Notch pathway. This system should prove useful for the investigation of the role of Mam within the Notch pathway.

The Notch locus is one of the best characterized loci in Drosophila melanogaster in terms of its genetic structure and developmental effects. Mutations in this locus profoundly affect the differentiation of the early embryo. Using an inversion involving the Notch locus and previously cloned sequences, we have isolated chromosomal segments from the Notch region (3C7) encompassing 80 kilobases (kb) of DNA. Based on comparison between mutant and wild-type DNA, we have positioned cloned sequences within the Notch genetic map; furthermore, we have defined a region of approximately 40 kb within which the structural lesions correlating with all Notch alleles mapped to date appear to reside. We have examined the transcriptional activity of the cloned sequences during ontogeny and find a single size class of poly(A)+ RNA, 10.5 kb long, that is homologous to sequences within this 40-kb region. We conclude that DNA sequences belonging to the Notch locus have been cloned and that the 10.5-kb poly(A)+ RNA is essential for wild-type Notch function. We discuss these structural and transcriptional data in light of the existing genetic and developmental characterization of the Notch locus.