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 p henotypes, similar to the eye phenotypes associated with loss-of-funct ion mutations of either Notch or Delta, Consistent with the notion tha t the truncated ligands reduce Notch signalling activity, the eye phen otypes of sev-DlTM and sev-SerTM are enhanced by loss-of-function muta tions 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 express ion of Enhancer of split m delta, a target of Notch signalling, is dow n-regulated by the truncated ligands highly expressed in neighbouring cells, We conclude that the truncated ligands act as antagonists of No tch signalling.