Several lines of evidence suggest an interplay between apical-basal polarity (ABP) and Notch (N) signaling in epithelia. Available data indicate that modulation of N signaling can occur through both direct regulation of the activity and mislocalization of either the receptor or the ligand. The purpose of this project is to understand how N activity can be modulated by differential regulation of apical-basal components or, in general, subcellular domains. A genetic screen among genes involved in ABP, ranging from regulators of vesicular trafficking or protein sorting to polarity regulators themselves, will help us identify the components underlying this modulation. Further genetic analysis together with molecular biology and biochemistry studies will help understand the molecular mechanisms of N activity modulation by ABP. Both ABP regulators and N pathway members have been shown to be involved in crucial events during development and tissue homeostasis, such as control of epithelial integrity and cell division, that, when distorted, can lead to tissue overgrowth and eventually cancer. Nevertheless, the molecular mechanisms underlying these processes are very poorly understood. This project will help shed light on these mechanisms.