Abstract
Abstract
Cell diversity generation is cardinal to the development of the functional central nervous system. The Notch pathway plays an important role in neurogenesis, spanning cell fate determination, cell death, and neural stem cell (NSC) competence switching, and is therefore highly regulated within cells. While the phosphorylation-based regulation of the pathway and its associated kinases is known, few phosphatases have been identified to counterbalance these regulations. Protein Phosphatase 1 is a member of a Serine/Threonine family of phosphatases responsible for a large majority of dephosphorylation events in the cell. In this study, we identify PP1-α and its regulatory subunit, PNUTS, as novel regulators of the Notch signalling pathway during
Drosophila
neurogenesis. We show that PP1-α87B/PNUTS positively regulate Notch signalling by dephosphorylating a highly conserved Serine residue in Su(H) to restore its DNA binding activity and thereby activating Notch downstream targets during neurogenesis. This facilitates the execution of two distinct physiological events, NSC apoptosis and competence switching, in different regions of the
Drosophila
CNS. We find that this regulation of the Notch pathway is also extendable to another cellular context, epithelial wing disc tissue, and critically relies on the phosphatase activity of PP1. Given that we can rescue the Notch-dependent depletion phenotypes of PP1-α using its human ortholog, we believe this regulation is likely to be conserved across species during development.