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Fumio MATSUZAKI, Ph. D. 
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, huge number of neural
cells are 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 homologs 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.
