Cell Division Dynamics Unit (Tomomi Kiyomitsu)

Research interests

During development of multi-cellular organisms, a fertilized egg undergoes repeated cell division called mitosis. In mitosis, a microtubule-based mitotic spindle is assembled and accurately segregates duplicated chromosomes to daughter cells to maintain genomic information (The spindle and chromosomes are shown in green and magenta, respectively, in the top movie). On the other hand, position and orientation of the mitotic spindle are related to cellular differentiation and tissue morphogenesis during development. Key conserved genes required for mitotic spindle assembly and positioning have been identified in simple model systems. However, their precise mechanisms are still unclear at the molecular and structural level. In additon, considering different features of early embryonic divisions in vertebrates, ealy embryos may have developed unique mechanisms for spindle assembly and positioning. 

In the Cell Division Dynamics Unit, we are studying the mechanisms of mitotic spindle assembly, positioning, and remodeling using cultured human cells and medaka fish embryos to understand the general and context-dependent mechanisms for chromosomal stability and cell fate regulation in vertebrate mitosis.

 

Experimental systems

We have mainly used symmetrically-dividing cultured human cells as a model. Recently, we are also using Medaka fish early embryos to reveal unidentified mechanisms of rapid spindle assembly and positioning in large early embryonic cells. We may also introduce other systems, such as mouse stem cells, to understand the roles of spindle positioning in self-renewal and differentiation.

 

 

 

Key technologies

We combine multiple advanced cell-biological technologies, including genome editing, multi-color live cell imaging, acute protein depletion (Tsuchiya et al., Current Biology 2021), and light-inducible protein manipulation (Okumura et al., eLife 2018). In addition, we will take advantage of OIST strengths, including high-end imaging and proteomics.

 

 

 

Key publications

1. Kiyomitsu A, Nishimura T, Hwang SJ, Ansai S, Kanemaki MT, Tanaka M, Kiyomitsu T.　Ran-GTP assembles a specialized spindle structure for accurate chromosome segregation in medaka early embryos Nature Communications 15(1):981. (2024)  doi: 10.1038/s41467-024-45251-w

2. Tsuchiya K, Hayashi H, Nishina M, Okumura M, Sato Y, Kanemaki MT, Goshima G, Kiyomitsu T* Ran-GTP is non-essential to activate NuMA for spindle pole focusing, but dynamically polarizes HURP near chromosomes. Current Biology 31(1):115-127.e3. (2021)

3. Okumura M, Natsume T, Kanemaki MT, Kiyomitsu T* Dynein-Dynactin-NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble. eLife doi: 10.7554/eLife.36559 (2018)

4. Natsume T, Kiyomitsu T, Saga Y, and Kanemaki MT* Rapid protein depletion in human cells by auxin-inducible degron tagging with short homology donors. Cell Reports 15(1):210-8. (2016)

5. Kiyomitsu T*, and Cheeseman IM* Cortical dynein and asymmetric membrane elongation coordinately position the spindle in anaphase. Cell 154(2):391-402. (2013)

6. Kiyomitsu T, and Cheeseman IM* Chromosome and spindle pole-derived signals generate an intrinsic code for spindle position and orientation. Nature Cell Biology 14(3):311-7 (2012)

 

Review

1. Kiyomitsu T*, and Boerner S. The Nuclear Mitotic Apparatus (NuMA) Protein: A Key Player for Nuclear Formation, Spindle Assembly, and Spindle Positioning Frontiers in Cell and Developmental Biology 9:653801 (2021)

2. Kiyomitsu T* The cortical force-generating machinery: how cortical spindle-pulling forces are generated. Current Opinion in Cell Biology 60:1-8 (2019)

3. Kiyomitsu T* Mechanisms of daughter cell-size control during cell division. Trends in Cell Biology 25(5):286-295. (2015)

 

*Positions for postdocs and graduate students are OPEN!*

We are looking for motivated postdocs and graduate students who would like to join us on our quest to unravel the basic mechanisms of cell division with cutting-edge technologies.

Please feel free to contact us (e-mail: tomomi.kiyomitsu[at]oist.jp) if you are interested.