Drosophila EHBP1 regulates Scabrous secretion during Notch-mediated lateral inhibition.

Notch signaling is an evolutionarily conserved pathway that plays a central role in numerous developmental and disease processes. The versatility of the Notch pathway relies on the activity of context-dependent regulators. These include rab11, sec15, arp3 and Drosophila EHBP1 (dEHBP1), which control Notch signaling and cell fate acquisition in asymmetrically dividing mechanosensory lineages by regulating the trafficking of the ligand Delta. Here, we show that dEHBP1 also controls the specification of R8 photoreceptors, as its loss results in the emergence of supernumerary R8 photoreceptors. Given the requirements for Notch signaling during lateral inhibition, we propose that dEHBP1 regulates distinct aspects of Notch signaling in different developmental contexts. We show that dEHBP1 regulates the exocytosis of Scabrous, a positive regulator of Notch signaling. In conclusion, dEHBP1 provides developmental versatility of intercellular signaling by regulating the trafficking of distinct Notch signaling components.