Cross-talk between Notch and TNF signalling pathways: role of dTraf1. (360G-Wellcome-083576_Z_07_Z)

SUMMARY Signalling between cells and tissues is critical for their development and for their continued modulation post-embryonically. Several key signalling pathways, which include the Notch pathway, have been implicated in mediating this communication during development. In contrast, other pathways, notably the pro-inflammatory Tumour necrosis factor (TNF), have predominantly been considered in the context of the immune response and tissue homeostasis. From our investigations into targets of N otch activation we have found that dTraf1, a key signalling adaptor for the TNF receptor is up-regulated following Notch activation, suggesting a potential link between Notch and TNF pathways. This raises questions about the contribution of dTraf1 and the TNF pathway to developmental patterning and conversely about the contribution of Notch to modulation of the immune response. Here we propose to investigate these questions, using Drosophila melanogaster as a model. AIMS The aims of our prop osed research are 1. To determine the extent of cross-talk between Notch and dTraf1 and its consequences; 2 To ascertain the roles of dTraf1 in developmental signalling and its relationship to TNF/TNR signalling; 3. To identify domains in dTraf1 required for its function and localisation in different signalling contexts.