Rusan, N. M. & Peifer, M. A role for a novel centrosome cycle in asymmetric cell divison. J. Cell Biol. 177, 13-20

Department of Biology and 2Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
The Journal of Cell Biology (Impact Factor: 9.83). 04/2007; 177(1):13-20. DOI: 10.1083/jcb.200612140
Source: PubMed


Tissue stem cells play a key role in tissue maintenance. Drosophila melanogaster central brain neuroblasts are excellent models for stem cell asymmetric division. Earlier work showed that their mitotic spindle orientation is established before spindle formation. We investigated the mechanism by which this occurs, revealing a novel centrosome cycle. In interphase, the two centrioles separate, but only one is active, retaining pericentriolar material and forming a "dominant centrosome." This centrosome acts as a microtubule organizing center (MTOC) and remains stationary, forming one pole of the future spindle. The second centriole is inactive and moves to the opposite side of the cell before being activated as a centrosome/MTOC. This is accompanied by asymmetric localization of Polo kinase, a key centrosome regulator. Disruption of centrosomes disrupts the high fidelity of asymmetric division. We propose a two-step mechanism to ensure faithful spindle positioning: the novel centrosome cycle produces a single interphase MTOC, coarsely aligning the spindle, and spindle-cortex interactions refine this alignment.

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    • "In contrast, in Drosophila neuroblasts, the daughter centrosome remains trapped near the neuroblast apical cortex while the differentiated Ganglion Mother Cell inherits the mother centrosome [47]. In this case, the daughter centriole, in which the protein centrobin is exclusively found, retains most of the pericentriolar material and most of the MTOC activity at the onset of mitosis [74] [79]. "
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    ABSTRACT: The centrosome position is tightly regulated during the cell cycle and during differentiated cellular functions. Because centrosome organizes the microtubule network to coordinate both intracellular organization and cell signaling, centrosome positioning is crucial to determine either the axis of cell division, the direction of cell migration or the polarized immune response of lymphocytes. Since alteration of centrosome positioning affects specific cell and tissue functions and seems to promote cell transformation and tumor spreading, the molecular mechanisms controlling centrosome movement in response to extracellular and intracellular cues are under intense investigation. Evolutionary conserved pathways involving polarity proteins and cytoskeletal rearrangements are emerging as common regulators of centrosome positioning in a wide variety of cellular contexts.
    Experimental Cell Research 10/2014; 328(2):240–248. DOI:10.1016/j.yexcr.2014.09.004 · 3.25 Impact Factor
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    • "Interestingly, the two centrosomes also behave differently during asymmetric division of neuroblasts. After centriole duplication at interphase, the two centrioles split and are functionally different [43,44]. The daughter centriole is active and retains PCM, thus becoming a MTOC of the cell [43–45]. "
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    ABSTRACT: Drosophila larval brain stem cells (neuroblasts) have emerged as an important model for the study of stem cell asymmetric division and the mechanisms underlying the transformation of neural stem cells into tumor-forming cancer stem cells. Each Drosophila neuroblast divides asymmetrically to produce a larger daughter cell that retains neuroblast identity, and a smaller daughter cell that is committed to undergo differentiation. Neuroblast self-renewal and differentiation are tightly controlled by a set of intrinsic factors that regulate asymmetric cell division (ACD). Any disruption of these two processes may deleteriously affect the delicate balance between neuroblast self-renewal and progenitor cell fate specification and differentiation, causing neuroblast overgrowth and ultimately lead to tumor formation in the fly. In this review, we discuss the mechanisms underlying Drosophila neural stem cell self-renewal and differentiation. Furthermore, we highlight emerging evidence in support of the notion that defects in asymmetric cell division in mammalian systems may play significant roles in the series of pathogenic events leading to the development of brain cancers.
    Bioscience Reports 06/2014; 34(4). DOI:10.1042/BSR20140008 · 2.64 Impact Factor
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    • "In Drosophila Nbs, unlike most cell types, the centrosomes split and start to separate immediately after cytokinesis (Rebollo et al., 2007; Rusan and Peifer, 2007). The daughter centrosome is immobile, retains Mt nucleation activity, and is connected to the apical cortex, whereas the mother centrosome displays weak Mt nucleation and migrates to the opposite side of the cell. "
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    ABSTRACT: The mitotic spindle is crucial to achieve segregation of sister chromatids. To identify new mitotic spindle assembly regulators, we isolated 855 microtubule-associated proteins (MAPs) from Drosophila melanogaster mitotic or interphasic embryos. Using RNAi, we screened 96 poorly characterized genes in the Drosophila central nervous system to establish their possible role during spindle assembly. We found that Ensconsin/MAP7 mutant neuroblasts display shorter metaphase spindles, a defect caused by a reduced microtubule polymerization rate and enhanced by centrosome ablation. In agreement with a direct effect in regulating spindle length, Ensconsin overexpression triggered an increase in spindle length in S2 cells, whereas purified Ensconsin stimulated microtubule polymerization in vitro. Interestingly, ensc-null mutant flies also display defective centrosome separation and positioning during interphase, a phenotype also detected in kinesin-1 mutants. Collectively, our results suggest that Ensconsin cooperates with its binding partner Kinesin-1 during interphase to trigger centrosome separation. In addition, Ensconsin promotes microtubule polymerization during mitosis to control spindle length independent of Kinesin-1.
    The Journal of Cell Biology 03/2014; 204(7):1111-21. DOI:10.1083/jcb.201311094 · 9.83 Impact Factor
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