In Drosophila melanogaster, genetic analysis has revealed several additional components of the N pathway including two ligands Delta(DL) and Serrate(SER), as well as cytoplasmic and nuclear proteins that cooperate to send extracellular signals to the nucleus (reviewed by Artavanis-Tsakonas et al., 1995). The receptor in this pathway is encoded by the Notch ( N) gene and is a transmembrane protein bearing tandem Epidermal Growth Factor (EGF)-like repeats in its extracellular domain and CDC10 repeats in its intracellular domain ( Wharton et al., 1985). The Notch signalling pathway defines an evolutionarily conserved cell interaction mechanism that controls diverse cellfate choices ( Artavanis-Tsakonas et al., 1995). We conclude that the truncated ligands act as antagonists of Notch signalling. These observations were extended to the molecular level by demonstrating that the expression of Enhancer of split mδ, a target of Notch signalling, is down-regulated by the truncated ligands highly expressed in neighbouring cells. Consistent with the notion that the truncated ligands reduce Notch signalling activity, the eye phenotypes of sevDlTM 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. 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. 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.
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