SECRETED FORMS OF DELTA AND SERRATE DEFINE ANTAGONISTS OF NOTCH SIGNALING IN DROSOPHILA

We examined the function of secreted forms of the two known Drosophila Notch ligands, DELTA and SERRATE, by expressing them under various pr omoters in the Drosophila developing eye and wing. The phenotypes asso ciated with the expression of secreted Delta (DlS) or secreted Serrate (SerS) forms mimic loss-of-function mutations in the Notch pathway. B oth genetic interactions between DlS or SerS transgenics and duplicati ons or loss-of-function mutations of Delta or Serrate indicate that Dl S and SerS behave as dominant negative mutations, These observations w ere extended to the molecular level by demonstrating that the expressi on of Enhancer of split m delta, a target of Notch signaling, is down- regulated by SERS, The antagonistic nature of the two mutant secreted ligand forms in the eye is consistent with their behavior in the wing, where they are capable of down-regulating wing margin specific genes opposite to the effects of the endogenous ligands. This analysis uncov ers secreted molecular antagonists of Notch signaling and provides evi dence of qualitative differences in the actions of the two ligands DLS and SERS.