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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Animals, Genetically Modified
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Basic Helix-Loop-Helix Transcription Factors
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Calcium-Binding Proteins
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Cell Division
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics
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Drosophila / genetics
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Drosophila / physiology*
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Drosophila Proteins*
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Eye / embryology
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Eye Proteins / genetics
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Female
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Insect Hormones / biosynthesis
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Insect Hormones / genetics
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Jagged-1 Protein
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Ligands
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Male
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Membrane Glycoproteins / genetics
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Membrane Proteins / physiology*
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Molecular Sequence Data
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Mutagenesis
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Promoter Regions, Genetic
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Receptor Protein-Tyrosine Kinases*
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Receptors, Notch
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Recombinant Fusion Proteins
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Repressor Proteins*
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Serrate-Jagged Proteins
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Signal Transduction
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Calcium-Binding Proteins
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DNA-Binding Proteins
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Drosophila Proteins
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E(spl)mdelta-HLH protein, Drosophila
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Eye Proteins
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Insect Hormones
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Jagged-1 Protein
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Ligands
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Membrane Glycoproteins
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Membrane Proteins
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N protein, Drosophila
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Receptors, Notch
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Recombinant Fusion Proteins
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Repressor Proteins
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Ser protein, Drosophila
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Serrate-Jagged Proteins
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delta protein
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Receptor Protein-Tyrosine Kinases
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sev protein, Drosophila