Cell Division Dynamics Unit (Tomomi Kiyomitsu)
We study the mechanisms of cell division, especially the regulatory mechanisms of symmetric cell division in vertebrate mitosis, using advanced cell-biological approaches.
During the development of multicellular organisms, cells divide symmetrically or asymmetrically to generate identical or different daughter cells, respectively. The balance between symmetric and asymmetric division is critical for cellular patterning, tissue morphogenesis and development. Prior studies demonstrated that mitotic spindle positioning defines cell division symmetry and asymmetry. However, how spindle positioning is mechanistically regulated by intrinsic and extrinsic signals remains poorly understood, especially in developmental contexts.
We previously demonstrated that mitotic human cells have developed intrinsic spindle centering systems that precisely position the spindle in the center of the mother cell to generate identical daughters for symmetric division (Kiyomitsu and Cheeseman, Nature Cell Biology 2012, Cell 2013). In addition, using advanced genetic and optogenetic technologies, we recently identified a core functional unit of the cortical force-generating machinery that controls spindle positioning in mitotic human cells (Okumura et al., eLife 2018).
At OIST, we aim to establish the molecular mechanisms of spindle centering and cortical force generation by combining multiple advanced technologies. In addition, we aim to further advance our understanding of how symmetric cell division is achieved and how the system is affected by intrinsic and extrinsic factors such as aging and environmental stress in self-renewing stem cells and early fish (Medaka) embryos.
Kiyomitsu, T. The cortical force-generating machinery: How cortical spindle-pulling forces are generated. Curr Opin Cell Biol. 2019 Apr 4;60:1-8. Review.
Okumura, M. Natsume, T. Kanemaki, M.T. Kiyomitsu, T. Dynein-Dynactin-NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble. eLife. 2018 May 31;7. pii: e36559.
Kiyomitsu, T. and Cheeseman, I.M. Cortical dynein and asymmetric membrane elongation coordinately position the spindle in anaphase. Cell. 2013 Jul 18; 154(2):391-402.
Kiyomitsu, T. and Cheeseman, I.M. Chromosome and spindle pole-derived signals generate an intrinsic code for spindle position and orientation. Nature Cell Biology. 2012 Feb 12;14(3):311-7.
Our paper was accepted for publication in Current Biology!
Tsuchiya, K. Hayashi, H. Nishina, M. Okumura, M. Sato, Y. Kanemaki, M.T. Goshima, G. Kiyomitsu, T. Ran-GTP is non-essential to activate NuMA for spindle pole focusing, but dynamically polarizes HURP near chromosomes.