The Abruptex domain of Notch regulates negative interactions between Notch, its ligands and Fringe

The Notch signalling pathway regulates cell fate choices during both verteb rate and invertebrate development. In the Drosophila wing disc, the activat ion of Notch by its ligands Delta and Serrate is required to make the dorso ventral boundary, where several genes, such as wingless and cut, are expres sed in a 2- to 4-cell-wide domain. The interactions between Notch and its l igands are modulated by Fringe via a mechanism that may involve post-transc riptional modifications of Notch, The ligands themselves also help to restr ict Notch activity to the dorsoventral boundary cells, because they antagon ise the activation of the receptor in the cells where their expression is h igh, This function of the ligands is critical to establish the polarity of signalling, but very little is known about the mechanisms involved in the i nteractions between Notch and its ligands that result in suppression of Not ch activity, The extracellular domain of Notch contains an array of 36 EGF repeats, two of which, repeats 11 and 12, are necessary for direct interact ions between Notch with Delta and Serrate, We investigate here the function of a region of the Notch extracellular domain where several missense mutat ions, called Abruptex, are localised, These Notch alleles are characterised by phenotypes opposite to the loss of Notch function and also by complex c omplementation patterns, We find that, in Abruptex mutant discs, only the n egative effects of the ligands and Fringe are affected, resulting in the fa ilure to restrict the expression of cut and wingless to the dorsoventral bo undary, We suggest that Abruptex alleles identify a domain in the Notch pro tein that mediates the interactions between Notch, its ligands and Fringe t hat result in suppression of Notch activity.