Secreted forms of DELTA and SERRATE define antagonists of Notch signaling in Drosophila.
We examined the function of secreted forms of the two known Drosophila Notch ligands, DELTA and SERRATE, by expressing them under various promoters in the Drosophila developing eye and wing. The phenotypes associated with the expression of secreted Delta (DlS) or secreted Serrate (SerS) forms mimic loss-of-function mutations in the Notch pathway. Both genetic interactions between DlS or SerS transgenics and duplications or loss-of-function mutations of Delta or Serrate indicate that DlS and SerS behave as dominant negative mutations. These observations were extended to the molecular level by demonstrating that the expression of Enhancer of split mdelta, a target of Notch signaling, is down-regulated by SERS. The antagonistic nature of the two mutant secreted ligand forms in the eye is consistent with their behavior in the wing, where they are capable of down-regulating wing margin specific genes opposite to the effects of the endogenous ligands. This analysis uncovers secreted molecular antagonists of Notch signaling and provides evidence of qualitative differences in the actions of the two ligands DLS and SERS.
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Department of Cell Biology, Boyer Center for Molecular Medicine, Yale University, New Haven, Connecticut 06536-0812, USA.
Artavanis-Tsakonas
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D000818:Animals; D030801:Animals, Genetically Modified; D002135:Calcium-Binding Proteins; D015536:Down-Regulation; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins; D005123:Eye / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D011401:Promoter Regions, Genetic; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism
D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C000606278:Ser protein, Drosophila; D000072099:Serrate-Jagged Proteins; C064045:delta protein