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| Cell Asymmetry |
Our group seeks to explore the molecular mechanisms underlying the organization of cells into highly ordered structures in the developing brain, where neural stem cells generate a large number of neurons of different fates at appropriate points in time. Asymmetric cell division is thought to play an essential role in this process. We have focused our study on the roles of asymmetric division and cell polarity in neural precursor cells in invertebrate ( Drosophila ) and vertebrate (mouse) systems.
Asymmetric cell division, in which daughter cells of different types are produced, is a process fundamental to the generation of cells of divergent type during proliferation. This type of division requires the polarized organization of mitotic cells when it occurs cell-autonomously, and depends on asymmetric microenvironments when the process is non-cell-autonomous. Drosophila neural stem cells, called neuroblasts, provide an excellent model system for the investigation of fundamental aspects of asymmetric division, including the cell polarity that promotes it. Neuroblasts typically undergo asymmetric divisions to produce two daughter cells: another neuroblast, and a smaller ganglion mother cell (GMC) to which neural fate determinants such as Numb and the Prospero transcription factor are asymmetrically partitioned. However, we do not yet understand a number of fundamental aspects of the asymmetric division of neuroblasts, such as the mechanisms responsible for asymmetrically sorting cellular components to the cortex, maintaining the neuroblast's cell polarity, and producing the smaller daughter GMC. We are addressing these issues using genetic screens for mutations affecting the asymmetric division of neuroblasts. The vertebrate brain comprises a considerably larger number of neurons arranged in a vastly more complex functional network than that in Drosophila . However, in both vertebrate and Drosophila , this huge number of neural cells is generated from a relatively small number of neural stem cells. Previous work has shown that neural progenitor cells divide both asymmetrically and symmetrically to produce descendant neurons. Vertebrate homologues have been found for most of the components acting in the asymmetric division of Drosophila neuroblasts, but the modes and roles of asymmetric divisions in vertebrate neurogenesis remain incompletely understood. Furthermore, still little is known about how asymmetric division contributes to neuronal fate determination. We are investigating the problems of how asymmetric division is involved in neuronal fate decisions and in organizing the cellular architecture of the vertebrate brain. |
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Yoshiura S, et al. Tre1 GPCR signaling orients stem cell divisions in the Drosophila central nervous system. Dev Cell 22.79-91 (2012)
Kosodo Y, et al. Regulation of interkinetic nuclear migration by cell cycle-coupled active and passive mechanisms in the developing brain. EMBO J (2011)
Shitamukai A., et al. Oblique Radial Glial Divisions in the Developing Mouse Neocortex Induce Self-Renewing Progenitors outside the Germinal Zone That Resemble Primate Outer Subventricular Zone Progenitors. J Neurosci 31.3683-95 (2011)
Kitajima A, et al. Progenitor properties of symmetrically dividing Drosophila neuroblasts during embryonic and larval development. Dev Biol 347. 9-23 (2010)
Ogawa H, et al. Protein phosphatase 2A negatively regulates aPKC signaling by modulating phosphorylation of Par-6 in Drosophila neuroblast asymmetric divisions. J Cell Sci 122.3242-9 (2009)
Shioi G, et al. Structural basis for self-renewal of neural progenitors in cortical neurogenesis. Cereb Cortex 19 Suppl 1.i55-61 (2009)
Kawaguchi A, et al. Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis. Development 135. 3113-24 (2008)
Konno D, et al. Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nat Cell Biol 10. 93-101 (2008)
Matsuzaki F and Sampath K. Wiring the nervous system: from form to function. Development 134. 1819-22 (2007)
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