The intracellular deletions of Delta and Serrate define dominant negative forms of the Drosophila Notch ligands.
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.
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Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06536-0812, USA.
Artavanis-Tsakonas
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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
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