title: The intracellular deletions of Delta and Serrate define dominant negative forms of the Drosophila Notch ligands.
abstract: We examined the function of the intracellular domains of the two known Drosophila Notch ligands, Delta and Serrate, by expressing wild-type and mutant forms in the developing Drosophila eye under the sevenless promoter. The expression of intracellularly truncated forms of either Delta (sev-DlTM) or Serrate (sev-SerTM) leads to extra photoreceptor phenotypes, similar to the eye phenotypes associated with loss-of-function mutations of either Notch or Delta. Consistent with the notion that the truncated ligands reduce. Notch signalling activity, the eye phenotypes of sev-DlTM and sev-SerTM are enhanced by loss-of-function mutations in the Notch pathway elements, Notch, Delta, mastermind, deltex and groucho, but are suppressed by a duplication of Delta or mutations in Hairless, a negative regulator of the pathway. These observations were extended to the molecular level by demonstrating that the expression of Enhancer of split m delta, a target of Notch signalling, is down-regulated by the truncated ligands highly expressed in neighbouring cells. We conclude that the truncated ligands act as antagonists of Notch signalling.
authors: Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06536-0812, USA.
authors: X
authors: X
authors: Sun
authors: S
authors: S
authors: Artavanis-Tsakonas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins; D005123:Eye / Q000196:embryology; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D007301:Insect Hormones / Q000096:biosynthesis / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011401:Promoter Regions, Genetic; D020794:Receptor Protein-Tyrosine Kinases; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D007301:Insect Hormones; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D020794:Receptor Protein-Tyrosine Kinases; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D000072099:Serrate-Jagged Proteins; C084530:E(spl)mdelta-HLH protein, Drosophila; C497759:N protein, Drosophila; C000606278:Ser protein, Drosophila; C064045:delta protein; C056737:sev protein, Drosophila