Different modes of Notch activation and strength regulation in the spermathecal secretory lineage

The strength of Notch signaling contributes to pleiotropic actions of Notch; however, we do not yet have a full understanding of the molecular regulation of Notch-signaling strength. We investigated the mode of Notch activation in the binary fate specification in the Drosophila spermathecal linage where Notch is asymmetrically activated across three divisions to specify different cell fates. Using clonal analysis, we showed that Delta (Dl) served as the ligand for Notch in the first and second divisions. Dl and Serrate (Ser) functioned redundantly in the third division. Compared to the third division, cell-fate decision in the second division required a lower level of Suppressor of Hairless protein, and, consequently, a lower level of Notch signaling. Several Notch endosomal trafficking regulators differentially regulated Notch signaling between the second and third divisions. Here, we demonstrate that cell differentiation in spermathecae involves different Notch-activation modes, Notch-signaling strengths, and Notch-trafficking regulations. Thus, the Drosophila spermathecal lineage is an exciting model for probing the molecular mechanisms that modulate the Notch signaling pathway.