title: Engineered truncations in the Drosophila mastermind protein disrupt Notch pathway function.
abstract: 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.
authors.affiliation: Department of Biology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: W
authors.initials: W
authors.lastname: Helms
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Ammerman
authors.forename: A L
authors.initials: AL
authors.lastname: Parks
authors.forename: M A
authors.initials: MA
authors.lastname: Muskavitch
authors.forename: B
authors.initials: B
authors.lastname: Yedvobnick
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins; D005656:Fungal Proteins / Q000502:physiology; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D014921:Wings, Animal / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D019476:Insect Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C085316:mam protein, Drosophila