Notch signalling is traditionally mediated through direct interaction between the Notch receptor and its transmembrane ligands, presented on the surface of adjacent cells. While both canonical and non-canonical pathways activate Notch signalling in signal-receiving cells, it remains unclear whether Notch itself can function as a ligand to activate receptors in neighboring cells. Here, we report that in the Drosophila testis, Notch expressed in spermatogonial progenitors, functions as a ligand for the phagocytic receptor Draper on neighboring somatic cyst cells. This Reverse-Notch signalling triggers spontaneous elimination of germ cell progenitors. We show that Notch binds Draper directly via its extracellular domain, independent of canonical Notch pathway activation. Furthermore, manipulation of Notch signaling is dispensable for this process, indicating a ligand-only role for Notch. These findings redefine Notch as a bifunctional protein capable of acting as both receptor and ligand, expanding the conceptual framework of Notch signalling beyond its conventional unidirectional pathway.
Romi et al. (Mon,) studied this question.