N-myristoyl Transferase Maintains Type II Neuroblasts through Notch Signaling in Drosophila

The development of a complex nervous system relies on precisely regulated heterogeneity and population stability among multiple types of neural stem cells (NSCs). In Drosophila melanogaster, the larval NSCs consist of type I neuroblasts (I NBs) and type II neuroblasts (II NBs). While the division pattern of II NB lineages is similar to the cortical expansion of primates, the detailed mechanism governing their maintenance is still not completely understood. Here, we demonstrate that the N-myristoyl transferase (NMT) in Drosophila serves as a critical regulator to maintain II NBs identity through N-myristoylation. Mechanistically, NMT myristoylates the proteasome subunit P26s4 that negatively regulates Hairless, an antagonist of Notch, consequently sustaining normal Notch activity. In human brain organoids, the function of NMT is conserved in the maintenance and proliferation of NSCs. Overall, this research not only reveals significant roles of NMT and N-myristoylation in II NB maintenance but also highlights a novel mechanism of how post-translational modification (PTM) regulates the homeostasis among heterogeneous NSCs during neurogenesis.