Drosophila Orb2 contributes to neural stem cell centrosome asymmetry and cell growth.

The deregulation of neural stem cell (NSC) homeostasis underlies neurodevelopmental disorders and tumorigenesis. In the Drosophila larval brain, NSCs divide asymmetrically along an invariant apical-basal axis to yield a larger self-renewing stem cell and a smaller, differentiating sibling. NSC divisions are instructed by centrosomes, which recruit pericentriolar material (PCM) important for microtubule-organizing activity. During interphase, NSC centrosomes are defined by asymmetries in PCM composition and functional activity. These asymmetries help align the mitotic spindle and position the cleavage furrow. Here, we show that the conserved RNA-binding protein Orb2 is required to enrich Polo kinase, the master regulator of centrosome maturation, at centrosomes throughout the cell cycle. Loss of Polo correlates with compromised localization of downstream PCM effectors in orb2 NSCs. Despite these impairments, orb2 NSCs build and orient their spindles normally to complete asymmetric cell division. However, through live imaging and clonal analysis, we demonstrate that Orb2 is required to maintain proper cell size, as loss of orb2 yields significantly smaller NSCs and sibling cells. We further show that Orb2 supports the timely clearance of cortical myosin important for cleavage plane positioning. These data indicate that Orb2 promotes NSC centrosome maturation and size of the neural progenitors. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].