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Spindle Positioning and Cell Division in Caenorhabditis elegans

By M. van der Voet


During cell division a cell duplicates its genetic material and segregates one intact copy into each daughter cell. However, cell division has many aspects in addition to the propagation of the genome. For instance, some cells divide asymmetrically, which contributes to the generation of cell diversity and maintenance of stem cell populations throughout the development and life of the organism. Two different mechanisms of asymmetric cell division exist. In one case the fate of the daughter cells is established by contact with a niche, in the other case the fate of the daughter cells is established by an intrinsically asymmetric division of the mother cell. These latter intrinsically asymmetric divisions follow a strict developmental program and much of the machinery has been conserved from nematodes to mammals. The mechanisms for asymmetric cell division have been extensively studied in the embryos of the nematode Caenorhabditis elegans. In this thesis we provide a new insight in the regulation of asymmetric cell division during C. elegans meiosis and early embryogenesis. We demonstrate that the spindle-positioning protein LIN-5 forms a complex with the previously uncharacterized protein ASPM-1. This complex has a function at the spindle poles, which is distinct from the function of the LIN-5 complex at the cell-cortex. The ASPM-1 protein is conserved in vertebrates, where it is required for proper formation of the neocortex. Our identification of a functional protein complex of ASPM-1 and the spindle-positioning protein LIN-5 in C. elegans may advance our understanding of the function of human ASPM in neurogenesis. Another question that was addressed in the thesis is how cells can go through so many rounds of cell division, with correct timing and high accuracy. To find an answer we analyzed the mechanisms that control progression through mitosis. We analyzed the level of redundancy and the requirement for individual cyclins in C. elegans cell-cycle progression. In addition we verified the functional conservation of a human APC-subunit in C. elegans

Topics: Biologie, Caenorhabditis elegans, Development, Mitosis, Asymmetric cell division, Spindle, Neurogenesis, Microcephaly, Cell Cycle, Cyclins, APC
Publisher: Utrecht University
Year: 2010
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