Casein kinase 2 maintains the self-renewal of neural stem cells via prospero phosphorylation in Drosophila

Most neural stem cells (NSCs) maintain self-renewal to ensure proper development of central nervous system (CNS) until a specific time and undergo terminal differentiation after neurogenesis. However, the regulation of the NSC maintenance during brain development is not well understood. Our study reveals that casein kinase 2 (CK2) is essential for maintaining NB self-renewal in late larval stages in Drosophila. Deficiency of CK2 results in increased nuclear localization of the differentiation promoting factor Prospero (Pros), and consequently a significant reduction in NB number. Mechanistically, Pros is phosphorylated by CK2 and sequestered in the cytoplasm, which prevents premature differentiation of the NB in late larval stages. While in pupal stages, the developmentally declined expression of CK2 allows NBs to undergo terminal differentiation. Overall, our study uncovers a critical role of CK2 as a time switch on NB transition from self-renewal to differentiation, highlighting a novel mechanism of the temporal regulation of neurogenesis by post-translational modifications (PTMs).