Abstract: To maintain a balance of self-renewal versus neurogenesis, neural stem cells (NSCs) undergo repeated cycles of asymmetric cell division along an invariant polarity axis instructed by centrosomes. During interphase, the NSC centrosomes are defined by marked asymmetries in protein composition and functional activity as microtubule-organizing centers. Here, we show a conserved RNA-binding protein, Orb2, supports centrosome asymmetry in interphase NSCs. While Orb2 localizes to the active apical centrosome, it promotes the transient inactivation of the basal centrosome required for centrosome segregation and spindle morphogenesis. Orb2 is required cell autonomously within NSCs to support centrosome asymmetry and maintenance of the stem cell pool. Conversely, loss of orb2 manifests in microcephaly independent of Orb2 function in NSCs. We suggest Orb2 plays opposing roles in centrosome activation and inactivation, possibly through the translational regulation of multiple mRNA substrates. Bioinformatics uncovers a significant overlap among RNA targets between Drosophila Orb2 and human CPEB4, consistent with a conserved role for CPEB proteins in centrosome regulation and neurodevelopment.

Journal Link: 10.1101/2021.11.23.469707 Journal Link: Publisher Website Journal Link: Downaload PDF Journal Link: Google Scholar