title: SNARE-dependent signaling at the Drosophila wing margin.
abstract: The wing of Drosophila melanogaster has long been used as a model system to characterize intermolecular interactions important in development. Implicit in our understanding of developmental processes is the proper trafficking and sorting of signaling molecules, although the precise mechanisms that regulate membrane trafficking in a developmental context are not well studied. We have therefore chosen the Drosophila wing to assess the importance of SNARE-dependent membrane trafficking during development. N-Ethylmaleimide-sensitive fusion protein (NSF) is a key component of the membrane-trafficking machinery and we constructed a mutant form of NSF whose expression we directed to the developing wing margin. This resulted in a notched-wing phenotype, the severity of which was enhanced when combined with mutants of VAMP/Synaptobrevin or Syntaxin, indicating that it results from impaired membrane trafficking. Importantly, we find that the phenotype is also enhanced by mutations in genes for wingless and components of the Notch signaling pathway, suggesting that these signaling pathways were disrupted. Finally, we used this phenotype to conduct a screen for interacting genes, uncovering two Notch pathway components that had not previously been linked to wing development. We conclude that SNARE-mediated membrane trafficking is an important component of wing margin development and that dosage-sensitive developmental pathways will act as a sensitive reporter of partial membrane-trafficking disruption.
authors.affiliation: Program in Developmental Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, M5G 1X8, Canada. bstewart@sickkids.on.ca
authors.forename: B A
authors.initials: BA
authors.lastname: Stewart
authors.forename: M
authors.initials: M
authors.lastname: Mohtashami
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.forename: W S
authors.initials: WS
authors.lastname: Trimble
authors.forename: G L
authors.initials: GL
authors.lastname: Boulianne
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004330:Drosophila / Q000033:anatomy & histology / Q000235:genetics / Q000254:growth & development*; D029721:Drosophila Proteins; D019476:Insect Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009154:Mutation; D052066:N-Ethylmaleimide-Sensitive Proteins; D010641:Phenotype; D021381:Protein Transport; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D051880:Receptors, Notch; D050600:SNARE Proteins; D015398:Signal Transduction; D014018:Tissue Distribution; D033921:Vesicular Transport Proteins; D014921:Wings, Animal / Q000033:anatomy & histology / Q000254:growth & development*
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D051880:Receptors, Notch; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; C498732:comt protein, Drosophila; D052066:N-Ethylmaleimide-Sensitive Proteins