Abstract
In multicellular organisms, cell-to-cell communication is critical for the regulation of tissue organization. Notch signaling relies on direct interactions between Notch receptors on signal-receiving cells and Notch ligands on adjacent cells. Notch evolved to mediate local cellular interactions that are responsive to spatial cues via dosage-sensitive short-lived signals. Immune cells utilize these unique properties of Notch signaling to direct their development, differentiation, and function. In this review, we explore how immune cells interact through Notch receptors with stromal cells in specialized niches of lymphohematopoietic organs that express Notch-activating ligands. We emphasize factors that control these interactions and focus on how Notch signals communicate spatial, quantitative, and temporal information to program the function of signal-receiving cells in the immune system.