Regulation of the asymmetric centrosome maturation cycle in neural stem cells. Dorothy A. Lerit, Nasser M. Rusan. Cell Biology and Physiology Center, NHLBI, National Institutes of Health, Bethesda, MD.

   Neuroblasts (NBs) are neural stem cells that invariantly divide along an apical-basal polarity axis during asymmetric cell division to produce one self-renewing NB and one smaller ganglion mother cell (GMC) fated for differentiation. The earliest known symmetry-breaking event in NBs is the docking of a single centrosome to the cortex, which defines the apical domain and precedes the localization of the determinants that impart the stem cell fate. Comprising an inner core of two centrioles surrounded by a cloud of pericentriolar material (PCM), centrosomes serve as the microtubule-organizing centers (MTOCs) of most eukaryotic cells. Strikingly, the duplicated interphase centrosomes of NBs are asymmetric. The apical centrosome is active, or mature, because it displays high PCM levels and MTOC activity, which facilitates cortical docking. In contrast, the other centrosome is inactive until just before mitotic onset. It has been proposed that inactivation is required for this centrosome to move to the basal cortex and orient the spindle axis. However, regulation of the asymmetric centrosome maturation cycle of NBs is little understood. Using mutant analysis, we have identified a novel mechanism required to establish asymmetries in NB centrosome activity. Our data indicate Drosophila Pericentrin-like protein (D-PLP) functions to establish centrosome asymmetry during interphase. Using quantitative analysis and live cell imaging, we show D-PLP affects the localization of several key PCM proteins and blocks the recruitment of the master regulator of centrosome maturation, Polo kinase, to the basal-fated centrosome. Loss of D-PLP results in two active interphase MTOCs and incomplete separation of the centrosomes to the distal poles. We find some NBs and GMCs inherit an aberrant centrosome number, which can be detrimental to the cell and tissue. These data suggest differential regulation of MTOC activity is required for proper centrosome segregation and support a model where the mechanism of centrosome maturation includes the removal of negative regulators of PCM recruitment.