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      Uncovering the link between malfunctions in Drosophila neuroblast asymmetric cell division and tumorigenesis

      review-article
      1 , 1 ,
      Cell & Bioscience
      BioMed Central
      Asymmetric cell division, Neuroblasts, Polarity, Determinants, Spindle orientation, Tumorigenesis

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          Abstract

          Asymmetric cell division is a developmental process utilized by several organisms. On the most basic level, an asymmetric division produces two daughter cells, each possessing a different identity or fate. Drosophila melanogaster progenitor cells, referred to as neuroblasts, undergo asymmetric division to produce a daughter neuroblast and another cell known as a ganglion mother cell (GMC). There are several features of asymmetric division in Drosophila that make it a very complex process, and these aspects will be discussed at length. The cell fate determinants that play a role in specifying daughter cell fate, as well as the mechanisms behind setting up cortical polarity within neuroblasts, have proved to be essential to ensuring that neurogenesis occurs properly. The role that mitotic spindle orientation plays in coordinating asymmetric division, as well as how cell cycle regulators influence asymmetric division machinery, will also be addressed. Most significantly, malfunctions during asymmetric cell division have shown to be causally linked with neoplastic growth and tumor formation. Therefore, it is imperative that the developmental repercussions as a result of asymmetric cell division gone awry be understood.

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          Most cited references77

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          The canonical Notch signaling pathway: unfolding the activation mechanism.

          Notch signaling regulates many aspects of metazoan development and tissue renewal. Accordingly, the misregulation or loss of Notch signaling underlies a wide range of human disorders, from developmental syndromes to adult-onset diseases and cancer. Notch signaling is remarkably robust in most tissues even though each Notch molecule is irreversibly activated by proteolysis and signals only once without amplification by secondary messenger cascades. In this Review, we highlight recent studies in Notch signaling that reveal new molecular details about the regulation of ligand-mediated receptor activation, receptor proteolysis, and target selection.
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            The cell biology of neurogenesis.

            During the development of the mammalian central nervous system, neural stem cells and their derivative progenitor cells generate neurons by asymmetric and symmetric divisions. The proliferation versus differentiation of these cells and the type of division are closely linked to their epithelial characteristics, notably, their apical-basal polarity and cell-cycle length. Here, we discuss how these features change during development from neuroepithelial to radial glial cells, and how this transition affects cell fate and neurogenesis.
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              Mechanisms of asymmetric stem cell division.

              Stem cells self-renew but also give rise to daughter cells that are committed to lineage-specific differentiation. To achieve this remarkable task, they can undergo an intrinsically asymmetric cell division whereby they segregate cell fate determinants into only one of the two daughter cells. Alternatively, they can orient their division plane so that only one of the two daughter cells maintains contact with the niche and stem cell identity. These distinct pathways have been elucidated mostly in Drosophila. Although the molecules involved are highly conserved in vertebrates, the way they act is tissue specific and sometimes very different from invertebrates.
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                Author and article information

                Journal
                Cell Biosci
                Cell Biosci
                Cell & Bioscience
                BioMed Central
                2045-3701
                2012
                14 November 2012
                : 2
                : 38
                Affiliations
                [1 ]Department of Biochemistry and Molecular Biology, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, 1425 San Pablo Street, Los Angeles, CA, 90033, USA
                Article
                2045-3701-2-38
                10.1186/2045-3701-2-38
                3524031
                23151376
                325a5f40-14c0-4767-855e-54183da2f2a7
                Copyright ©2012 Kelsom and Lu; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 September 2012
                : 5 November 2012
                Categories
                Review

                Cell biology
                asymmetric cell division,spindle orientation,tumorigenesis,determinants,neuroblasts,polarity

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