SEARCH
Search DetailsMOTEGI FUMIO
| Institute for Genetic Medicine Pathophysiology | Professor |
Researcher basic information
■ Degree■ URL
researchmap URLホームページURL■ Various IDs
Researcher number
- 10360653
Research KeywordResearch Field
- Life Science, Biophysics, Mechanobiology
- Life Science, Developmental biology, Embryogenesis
- Life Science, Cell biology, Cell polarity
- Master's degree program, Graduate School of Chemical Sciences and Engineering
- Doctoral (PhD) degree program, Graduate School of Chemical Sciences and Engineering
Career
■ CareerCareer
- Jan. 2022 - Present
Institute for Genetic Medicine, Hokkaido University, Developmental Physiology, Professor - Aug. 2012 - Mar. 2021
Dept. of Biological Sciences, Faculty of Science, National University of Singapore, Assistant Professor, Singapore - Aug. 2012 - Mar. 2021
Mechanobiology Institute, National University of Singapore, Principle Investigator, Singapore - Aug. 2012 - Mar. 2021
Temasek Lifesciences Laboratory, Senior Principle Investigator, Singapore - Aug. 2007 - Jul. 2012
Johns Hopkins University School of Medicine, Postdoctoral Researcher, United States - Aug. 2006 - Jul. 2007
UCSD, Postdoctoral Researcher, United States - Apr. 2002 - Jul. 2006
RIKEN Center for Developmental Biology, Postdoctoral Researcher, Japan
- Apr. 1997 - Mar. 2002, The University of Tokyo, Graduate School of Arts and Sciences, 生命環境科学系, Japan
- 2024 - 2026
日本細胞生物学会, 理事 - 2022 - 2024
日本細胞生物学会, 理事, Society - 2024
第32回日本バイオイメージング学会学術集会, 組織委員, Society - 2022
日本細胞生物学会, 日本細胞生物学会誌 Cell Structure and Function 編集委員(Associate Editor), Society - 2022
日本分子生物学会, 第45回日本分子生物学会年会 組織委員, Society
Research activity information
■ Awards- 2012, Singapore National Research Foundation, Singapore National Research Foundation Fellow
- May 2010, Japan Society for Cell Biology, Young Scientist Best Presentation Award
- Visualization and Analyses of Cytoplasmic Streaming in C. elegans Zygotes
Kenji Kimura; Fumio Motegi
Methods in Molecular Biology, 131, 139, Springer US, 01 Dec. 2024
In book - Cell polarity: Adapting the PAR cascade to diverse cellular contexts.
Kazunori Yamamoto; Fumio Motegi
Current biology : CB, 33, 20, R1047-R1049, 23 Oct. 2023, [International Magazine]
English, Scientific journal, Two new studies shed light on the intricacies of Caenorhabditis elegans embryo patterning, revealing how the conserved interaction and crosstalk of PAR proteins are adapted to perceive distinct cues, ultimately shaping unique asymmetries in form and function. - Fluid flow dynamics in cellular patterning.
Kenji Kimura; Fumio Motegi
Seminars in cell & developmental biology, 14 Jul. 2021, [International Magazine]
English, Scientific journal, The development of complex forms of multicellular organisms depends on the spatial arrangement of cellular architecture and functions. The interior design of the cell is patterned by spatially biased distributions of molecules and biochemical reactions in the cytoplasm and/or on the plasma membrane. In recent years, a dynamic change in the cytoplasmic fluid flow has emerged as a key physical process of driving long-range transport of molecules to particular destinations within the cell. Here, recent experimental advances in the understanding of the generation of the various types of cytoplasmic flows and contributions to intracellular patterning are reviewed with a particular focus on feedback mechanisms between the mechanical properties of fluid flow and biochemical signaling during animal cell polarization. - A balance between antagonizing PAR proteins specifies the pattern of asymmetric and symmetric divisions in C. elegans embryogenesis.
Yen Wei Lim; Fu-Lai Wen; Prabhat Shankar; Tatsuo Shibata; Fumio Motegi
Cell reports, 36, 1, 109326, 109326, 06 Jul. 2021, [International Magazine]
English, Scientific journal, Coordination between cell differentiation and proliferation during development requires the balance between asymmetric and symmetric modes of cell division. However, the cellular intrinsic cue underlying the choice between these two division modes remains elusive. Here, we show evidence in Caenorhabditis elegans that the invariable lineage of the division modes is specified by the balance between antagonizing complexes of partitioning-defective (PAR) proteins. By uncoupling unequal inheritance of PAR proteins from that of fate determinants during cell division, we demonstrate that changes in the balance between PAR-2 and PAR-6 can be sufficient to re-program the division modes from symmetric to asymmetric and vice versa in two daughter cells. The division mode adopted occurs independently of asymmetry in cytoplasmic fate determinants, cell-size asymmetry, and cell-cycle asynchrony between sister cells. We propose that the balance between PAR proteins represents an intrinsic self-organizing cue for the specification of the two division modes during development. - Mechanochemical Control of Symmetry Breaking in the Caenorhabditis elegans Zygote
Wan Jun Gan; Fumio Motegi
Frontiers in Cell and Developmental Biology, 8, Frontiers Media SA, 18 Jan. 2021
Scientific journal, Cell polarity is the asymmetric organization of cellular components along defined axes. A key requirement for polarization is the ability of the cell to break symmetry and achieve a spatially biased organization. Despite different triggering cues in various systems, symmetry breaking (SB) usually relies on mechanochemical modulation of the actin cytoskeleton, which allows for advected movement and reorganization of cellular components. Here, the mechanisms underlying SB inCaenorhabditis elegans zygote, one of the most popular models to study cell polarity, are reviewed. A zygote initiates SB through the centrosome, which modulates mechanics of the cell cortex to establish advective flow of cortical proteins including the actin cytoskeleton and partitioning defective (PAR) proteins. The chemical signaling underlying centrosomal control of the Aurora A kinase–mediated cascade to convert the organization of the contractile actomyosin network from an apolar to polar state is also discussed. - Novel approaches to link apicobasal polarity to cell fate specification
Fumio Motegi; Nicolas Plachta; Virgile Viasnoff
Current Opinion in Cell Biology, 62, 78, 85, Elsevier BV, Feb. 2020
Scientific journal - Aurora-A Breaks Symmetry in Contractile Actomyosin Networks Independently of Its Role in Centrosome Maturation
Peng Zhao; Xiang Teng; Sarala Neomi Tantirimudalige; Masatoshi Nishikawa; Thorsten Wohland; Yusuke Toyama; Fumio Motegi
Developmental Cell, 48, 5, 631, 645.e6, Elsevier BV, Mar. 2019
Scientific journal - Establishment of the PAR-1 cortical gradient by the aPKC-PRBH circuit
Ravikrishna Ramanujam; Ziyin Han; Zhen Zhang; Pakorn Kanchanawong; Fumio Motegi
Nature Chemical Biology, 14, 10, 917, 927, Springer Science and Business Media LLC, Oct. 2018
Scientific journal - TPXL-1 activates Aurora A to clear contractile ring components from the polar cortex during cytokinesis
Sriyash Mangal; Jennifer Sacher; Taekyung Kim; Daniel Sampaio Osório; Fumio Motegi; Ana Xavier Carvalho; Karen Oegema; Esther Zanin
Journal of Cell Biology, 217, 3, 837, 848, Rockefeller University Press, 05 Mar. 2018
Scientific journal, During cytokinesis, a signal from the central spindle that forms between the separating anaphase chromosomes promotes the accumulation of contractile ring components at the cell equator, while a signal from the centrosomal microtubule asters inhibits accumulation of contractile ring components at the cell poles. However, the molecular identity of the inhibitory signal has remained unknown. To identify molecular components of the aster-based inhibitory signal, we developed a means to monitor the removal of contractile ring proteins from the polar cortex after anaphase onset. Using this assay, we show that polar clearing is an active process that requires activation of Aurora A kinase by TPXL-1. TPXL-1 concentrates on astral microtubules coincident with polar clearing in anaphase, and its ability to recruit Aurora A and activate its kinase activity are essential for clearing. In summary, our data identify Aurora A kinase as an aster-based inhibitory signal that restricts contractile ring components to the cell equator during cytokinesis. - ImaEdge – a platform for quantitative analysis of the spatiotemporal dynamics of cortical proteins during cell polarization
Zhen Zhang; Yen Wei Lim; Peng Zhao; Pakorn Kanchanawong; Fumio Motegi
Journal of Cell Science, 130, 24, 4200, 4212, The Company of Biologists, 15 Dec. 2017
Scientific journal - Forceful patterning in mouse preimplantation embryos
Ravikrishna Ramanujam; Tricia Yu Feng Low; Yen Wei Lim; Fumio Motegi
Seminars in Cell & Developmental Biology, 71, 129, 136, Elsevier BV, Nov. 2017
Scientific journal - Cortical forces and CDC-42 control clustering of PAR proteins for Caenorhabditis elegans embryonic polarization
Shyi-Chyi Wang; Tricia Yu Feng Low; Yukako Nishimura; Laurent Gole; Weimiao Yu; Fumio Motegi
Nature Cell Biology, 19, 8, 988, 995, Springer Science and Business Media LLC, Aug. 2017, [International Magazine]
English, Scientific journal, Cell polarization enables zygotes to acquire spatial asymmetry, which in turn patterns cellular and tissue axes during development. Local modification in the actomyosin cytoskeleton mediates spatial segregation of partitioning-defective (PAR) proteins at the cortex, but how mechanical changes in the cytoskeleton are transmitted to PAR proteins remains elusive. Here we uncover a role of actomyosin contractility in the remodelling of PAR proteins through cortical clustering. During embryonic polarization in Caenorhabditis elegans, actomyosin contractility and the resultant cortical tension stimulate clustering of PAR-3 at the cortex. Clustering of atypical protein kinase C (aPKC) is supported by PAR-3 clusters and is antagonized by activation of CDC-42. Cortical clustering is associated with retardation of PAR protein exchange at the cortex and with effective entrainment of advective cortical flows. Our findings delineate how cytoskeleton contractility couples the cortical clustering and long-range displacement of PAR proteins during polarization. The principles described here would apply to other pattern formation processes that rely on local modification of cortical actomyosin and PAR proteins. - Cortical Polarity of the RING Protein PAR-2 Is Maintained by Exchange Rate Kinetics at the Cortical-Cytoplasmic Boundary
Yukinobu Arata; Michio Hiroshima; Chan-Gi Pack; Ravikrishna Ramanujam; Fumio Motegi; Kenichi Nakazato; Yuki Shindo; Paul W. Wiseman; Hitoshi Sawa; Tetsuya J. Kobayashi; Hugo B. Brandão; Tatsuo Shibata; Yasushi Sako
Cell Reports, 17, 1, 316, 316, Elsevier BV, Sep. 2016, [International Magazine]
English, Scientific journal - Cortical Polarity of the RING Protein PAR-2 Is Maintained by Exchange Rate Kinetics at the Cortical-Cytoplasmic Boundary.
Yukinobu Arata; Michio Hiroshima; Chan-Gi Pack; Ravikrishna Ramanujam; Fumio Motegi; Kenichi Nakazato; Yuki Shindo; Paul W Wiseman; Hitoshi Sawa; Tetsuya J Kobayashi; Hugo B Brandão; Tatsuo Shibata; Yasushi Sako
Cell reports, 16, 8, 2156, 2168, 23 Aug. 2016, [International Magazine]
English, Scientific journal, Cell polarity arises through the spatial segregation of polarity regulators. PAR proteins are polarity regulators that localize asymmetrically to two opposing cortical domains. However, it is unclear how the spatially segregated PAR proteins interact to maintain their mutually exclusive partitioning. Here, single-molecule detection analysis in Caenorhabditis elegans embryos reveals that cortical PAR-2 diffuses only short distances, and, as a result, most PAR-2 molecules associate and dissociate from the cortex without crossing into the opposing domain. Our results show that cortical PAR-2 asymmetry is maintained by the local exchange reactions that occur at the cortical-cytoplasmic boundary. Additionally, we demonstrate that local exchange reactions are sufficient to maintain cortical asymmetry in a parameter-free mathematical model. These findings suggest that anterior and posterior PAR proteins primarily interact through the cytoplasmic pool and not via cortical diffusion. - The PAR network: redundancy and robustness in a symmetry-breaking system
Fumio Motegi; Geraldine Seydoux
Philosophical Transactions of the Royal Society B: Biological Sciences, 368, 1629, 20130010, 20130010, The Royal Society, 05 Nov. 2013
Scientific journal, To become polarized, cells must first ‘break symmetry’. Symmetry breaking is the process by which an unpolarized, symmetric cell develops a singularity, often at the cell periphery, that is used to develop a polarity axis. The
Caenorhabditis elegans
zygote breaks symmetry under the influence of the sperm-donated centrosome, which causes the PAR polarity regulators to sort into distinct anterior and posterior cortical domains. Modelling analyses have shown that cortical flows induced by the centrosome combined with antagonism between anterior and posterior PARs (mutual exclusion) are sufficient, in principle, to break symmetry, provided that anterior and posterior PAR activities are precisely balanced. Experimental evidence indicates, however, that the system is surprisingly robust to changes in cortical flows, mutual exclusion and PAR balance. We suggest that this robustness derives from redundant symmetry-breaking inputs that engage two positive feedback loops mediated by the anterior and posterior PAR proteins. In particular, the PAR-2 feedback loop stabilizes the polarized state by creating a domain where posterior PARs are immune to exclusion by anterior PARs. The two feedback loops in the PAR network share characteristics with the two feedback loops in the Cdc42 polarization network of
Saccharomyces cerevisiae
. - Microtubules induce self-organization of polarized PAR domains in Caenorhabditis elegans zygotes
Fumio Motegi; Seth Zonies; Yingsong Hao; Adrian A Cuenca; Erik Griffin; Geraldine Seydoux
Nature Cell Biology, 13, 11, 1361, 1367, Oct. 2011, [Peer-reviewed], [Lead author] - Basement membrane sliding and targeted adhesion remodels tissue boundaries during uterine–vulval attachment in Caenorhabditis elegans
Shinji Ihara; Elliott J. Hagedorn; Meghan A. Morrissey; Qiuyi Chi; Fumio Motegi; James M. Kramer; David R. Sherwood
Nature Cell Biology, 13, 6, 641, 651, Springer Science and Business Media LLC, Jun. 2011
Scientific journal - Cytoplasmic Partitioning of P Granule Components Is Not Required to Specify the Germline in C. elegans
C. M. Gallo; J. T. Wang; F. Motegi; G. Seydoux
Science, 330, 6011, 1685, 1689, American Association for the Advancement of Science (AAAS), 17 Dec. 2010
Scientific journal - Caenorhabditis elegans ortholog of the p24/p22 subunit, DNC-3, is essential for the formation of the dynactin complex by bridging DNC-1/p150(Glued) and DNC-2/dynamitin
Masahiro Terasawa; Mika Toya; Fumio Motegi; Miyeko Mana; Kuniaki Nakamura; Asako Sugimoto
Genes to Cells, 15, 11, 1145, 1157, Nov. 2010 - Symmetry breaking and polarization of the C. elegans zygote by the polarity protein PAR-2
S. Zonies; F. Motegi; Y. Hao; G. Seydoux
Development, 137, 10, 1669, 1677, The Company of Biologists, 15 May 2010
Scientific journal - A new mechanism controlling kinetochore-microtubule interactions revealed by comparison of two dynein-targeting components: SPDL-1 and the Rod/Zwilch/Zw10 complex
R. Gassmann; A. Essex; J.-S. Hu; P. S. Maddox; F. Motegi; A. Sugimoto; S. M. O'Rourke; B. Bowerman; I. McLeod; J. R. Yates; K. Oegema; I. M. Cheeseman; A. Desai
Genes & Development, 22, 17, 2385, 2399, Cold Spring Harbor Laboratory, 01 Sep. 2008
Scientific journal - Revisiting the role of microtubules in C. elegans polarity.
Motegi F; Seydoux G
Journal of Cell Biology, 179, 3, 367, 369, Nov. 2007 - Function of microtubules at the onset of cytokinesis
Fumio Motegi; Asako Sugimoto
Tanpakusitu Kakusan Koso, 51, 1590, 1595, Sep. 2006 - Sequential functioning of the ECT-2 RhoGEF, RHO-1 and CDC-42 establishes cell polarity in Caenorhabditis elegans embryos
Fumio Motegi; Asako Sugimoto
Nature Cell Biology, 8, 9, 978, 985, Springer Science and Business Media LLC, Sep. 2006
Scientific journal - Cell polarization: lessons from C. elegans asymmetric cell division
Fumio Motegi; Asako Sugimoto
Tanpakushitsu Kakusan Koso, 51, 776, 781, May 2006 - Two phases of astral microtubule activity during cytokinesis in C. elegans embryos
Motegi F; Velarde NV; Piano F; Sugimoto A
Developmental Cell, 10, 4, 509, 520, Apr. 2006 - Myosin-II reorganization during mitosis is controlled temporally by its dephosphorylation and spatially by Mid1 in fission yeast
Fumio Motegi; Mithilesh Mishra; Mohan K. Balasubramanian; Issei Mabuchi
Journal of Cell Biology, 165, 5, 685, 695, Rockefeller University Press, 07 Jun. 2004
Scientific journal, Cytokinesis in many eukaryotes requires an actomyosin contractile ring. Here, we show that in fission yeast the myosin-II heavy chain Myo2 initially accumulates at the division site via its COOH-terminal 134 amino acids independently of F-actin. The COOH-terminal region can access to the division site at early G2, whereas intact Myo2 does so at early mitosis. Ser1444 in the Myo2 COOH-terminal region is a phosphorylation site that is dephosphorylated during early mitosis. Myo2 S1444A prematurely accumulates at the future division site and promotes formation of an F-actin ring even during interphase. The accumulation of Myo2 requires the anillin homologue Mid1 that functions in proper ring placement. Myo2 interacts with Mid1 in cell lysates, and this interaction is inhibited by an S1444D mutation in Myo2. Our results suggest that dephosphorylation of Myo2 liberates the COOH-terminal region from an intramolecular inhibition. Subsequently, dephosphorylated Myo2 is anchored by Mid1 at the medial cortex and promotes the ring assembly in cooperation with F-actin. - Importance of a Myosin II-Containing Progenitor for Actomyosin Ring Assembly in Fission Yeast
Kelvin C.Y. Wong; Ventris M. D'souza; Naweed I. Naqvi; Fumio Motegi; Issei Mabuchi; Mohan K. Balasubramanian
Current Biology, 12, 9, 724, 729, Elsevier BV, Apr. 2002
Scientific journal - Contractile ring formation in Xenopus egg and fission yeast
Noguchi T; Arai R; Motegi F; Nakano K; Mabuchi I
Cell Structure and Function, 26, 6, 545, 554, Japan Society for Cell Biology, Dec. 2001
English, How actin filaments (F-actin) and myosin II (myosin) assemble to form the contractile ring was investigated with fission yeast and Xenopus egg. In fission yeast cells, an aster-like structure composed of F-actin cables is formed at the medial cortex of the cell during prophase to metaphase, and a single F-actin cable(s) extends from this structure, which seems to be a structural basis of the contractile ring. In early mitosis, myosin localizes as dots in the medial cortex independently of F-actin. Then they fuse with each other and are packed into a thin contractile ring.
At the growing ends of the cleavage furrow of Xenopus eggs, F-actin at first assembles to form patches. Next they fuse with each other to form short F-actin bundles. The short bundles then form long bundles. Myosin seems to be transported by the cortical movement to the growing end and assembles there as spots earlier than F-actin. Actin polymerization into the patches is likely to occur after accumulation of myosin. The myosin spots and the F-actin patches are simultaneously reorganized to form the contractile ring bundles.
The idea that a Ca signal triggers cleavage furrow formation was tested with Xenopus eggs during the first cleavage. We could not detect any Ca signals such as a Ca wave, Ca puffs or even Ca blips at the growing end of the cleavage furrow. Furthermore, cleavages are not affected by Ca-chelators injected into the eggs at concentrations sufficient to suppress the Ca waves. Thus we conclude that formation of the contractile ring is not induced by a Ca signal at the growing end of the cleavage furrow. - Identification of two type V myosins in fission yeast, one of which functions in polarized cell growth and moves rapidly in the cell.
Motegi F; Arai R; Mabuchi I
Molecular Biology of the Cell, 12, 5, 1367, 1380, May 2001 - Identification and functional analysis of the gene for type I myosin in fission yeast
Toya M; Motegi F; Nakano K; Mabuchi I; Yamamoto M
Genes to Cells, 62, 3, 187, 199, Mar. 2001 - The S. pombe rlc1 gene encodes a putative myosin regulatory light chain that binds the type II myosins myo3p and myo2p
Le Goff; Motegi F; Salimova E; Mabuchi I; Simanis V
113, 4157, 4163, Dec. 2000 - Molecular mechanism of myosin-II assembly at the division site in Schizosaccharomyces pombe
F Motegi; K Nakano; I Mabuchi
Journal of Cell Science, 113, 1813, 1825, May 2000 - Overproduction of elongation factor 1α, an essential translational component, causes aberrant cell morphology by affecting the control of growth polarity in fission yeast
Masako Suda; Mikiko Fukui; Yuki Sogabe; Kazuhito Sato; Akeshi Morimatsu; Ritsuko Arai; Fumio Motegi; Tokichi Miyakawa; Issei Mabuchi; Dai Hirata
Genes to Cells, 4, 9, 517, 527, Wiley, Sep. 1999
Scientific journal - Identification of Myo3, a second type-II myosin heavy chain in the fission yeast Schizosaccharomyces pombe
Fumio Motegi; Kentaro Nakano; Chikako Kitayama; Masayuki Yamamoto; Issei Mabuchi
FEBS Letters, 420, 2-3, 161, 166, Wiley, 29 Dec. 1997
Scientific journal
■ Lectures, oral presentations, etc.
- Collective induction of oogenesis via long-range cytoplasmic streaming in C. elegans
Fumio Motegi
第76回日本細胞生物学会大会, 2024, Oral presentation - Collective Induction of Oogenesis via Cytoplasmic Streaming in C. Elegans
Fumio Motegi
第57回日本発生生物学会, 2024, Invited oral presentation
[Invited] - Collective Induction of Oogenesis via Cytoplasmic Streaming in C. Elegans
Fumio Motegi
2024 Gordon Research Conference on Cell Polarity Signalling, 2024, Invited oral presentation
[Invited] - 力学と化学の連携による細胞パターン形成
茂木文夫
定量生物学の会第十一回年会, 2024, Invited oral presentation
[Invited] - Collective induction of oogenesis via long-range cytoplasmic streaming in C.elegans
Fumio Motegi
ASCB CELL BIO 2023, 2023, Invited oral presentation
[Invited] - 細胞パターニングにおける力学化学変換反応の制御
Fumio Motegi
日本機械学会 第35回バイオエンジニアリング講演会, 2023, Invited oral presentation
[Invited] - Introduction of multicellular mechanobiology research in Japan
Fumio Motegi
Engineering Mechanics of Cell and Tissue Morphogenesis 2022, 2022, Nominated symposium
[Invited] - Mechano-chemical feedbacks in embryonic patterning
Fumio Motegi
第45回日本分子生物学会年会, 2022, Invited oral presentation
[Invited] - 体細胞と生殖細胞の運命パターン秩序化
茂木文夫
生理学研究所・北海道大学遺伝子病制御研究 ジョイントシンポジウム リエゾンラボ炎症シンポジウム, 2022, Invited oral presentation
[Invited] - 細胞極性の脱構築と再構築
茂木文夫
第一回細胞分裂研究会, 2022, Invited oral presentation
[Invited] - Binary choice of asymmetric and symmetric cell divisions in C. elegans embryogenesis
Fumio Motegi
International joint symposium between Japan Society of developmental Biologists and Singapore Developmental Biology Society, 2021, Invited oral presentation
[Invited] - Construction and deconstruction of metazoan cell polarity.
Fumio Motegi
ICReDD-Hokkaido University Five Attached Institutes Joint Symposium, 2021, Invited oral presentation
[Invited] - Binary choice of asymmetric and symmetric cell divisions in C. elegans embryogenesis
Fumio Motegi
Singapore Developmental Biology Society monthly seminar, 2021, Invited oral presentation
[Invited] - Mechanical control of symmetry breaking in C. elegans embryo
Fumio Motegi
第73回日本細胞生物学会, 2021, Invited oral presentation
[Invited] - Mechano-Chemical Control of Symmetry Breaking in C. eleagns zygotes.
Fumio Motegi
The 15th international Symposium of the Institute Network for Biomedical Sciences, 2020, Keynote oral presentation
[Invited] - Mechanical Control of Symmetry Breaking in C. eleagns zygotes.
Fumio Motegi
The Mechanobiology Institute 2020 Virtual Conference, “From Molecules to Organs: The Mechanobiology of Morphogenesis”, 2020, Invited oral presentation
[Invited] - Deconstruction and reconstruction of cell polarity networks
Fumio Motegi
2nd Joint Symposium between MBI and UBI, 2019, Invited oral presentation
[Invited] - Aurora-A breaks symmetry in C. elegans zygotes independently of its role in centrosome maturation
Fumio Motegi
第52回日本発生生物学会年会, 2019, Oral presentation - Aurora-A breaks symmetry in C. elegans zygotes independently of its role in centrosome maturation
Fumio Motegi
The ASCB EMBO 2018 meeting, 2018, Invited oral presentation
[Invited] - 細胞が創る空間パターニングの脱構築と再構築
茂木文夫
第41 回日本分子生物学会年会, 2018, Invited oral presentation
[Invited] - Deconstruction and reconstruction of cell polarity networks
Fumio Motegi
第56 回日本生物物理学会年会, 2018, Invited oral presentation
[Invited] - Deconstruction and reconstruction of cell polarity networks
Fumio Motegi
第70回日本細胞生物学会・第51回日本発生生物学会合同大会(APDBN共催), 2018, Invited oral presentation
[Invited] - Deconstruction and Reconstruction of C. elegans PAR Polarity
Fumio Motegi
The Gordon Research Conference on Cell Polarity, 2018, Invited oral presentation
[Invited] - Local and global remodelling of cortical myosin by the mitotic kinase Aurora-A
Fumio Motegi
International Symposium on Mechanobiology, 2017, Invited oral presentation
[Invited] - Reconstitution of the PAR polarity networks in a heterologous cell system
Fumio Motegi
21st International C. elegans Meeting, 2017, Oral presentation - 細胞膜張力に依存したPAR複合体のナノスケールクラスター形成
Fumio Motegi
第69 回日本細胞生物学会年会, 2017, Invited oral presentation
[Invited] - Cortical contractility induces clustering of PAR proteins for embryonic polariza
Fumio Motegi
第39 回日本分子生物学会年会, 2016, Invited oral presentation
[Invited] - The robust landscape of embryonic PAR polarity controls cellular decisions
Fumio Motegi; Yen Wei Lim
THE ALLIED GENETICS CONFERENCE 2016, 2016, Keynote oral presentation
[Invited] - Symmetry breaking: lessons from C. elegans zygote
Fumio Motegi
Joint symposium of Curie Institute and Mechanobiology Institute, 2016, Invited oral presentation
[Invited] - Dual mechanisms for ensuring the posterior PAR gradient in C. elegans zygote
Fumio Motegi
Mechanobiology of Development and Multicellular Dynamics, 2014, Invited oral presentation
[Invited] - Dual mechanisms for ensuring the posterior PAR gradient
Fumio Motegi
The 6th Asia-Pacific C. elegans Meeting, 2014, Oral presentation - Dual mechanisms for ensuring the posterior PAR gradient
Fumio Motegi
The Gordon Research Conference on Cell Polarity, 2014, Invited oral presentation
[Invited] - Symmetry breaking in C. elegans zygote
Fumio Motegi
Asia Pacific Organization of Cell Biology 7th Congress and ASCB Workshops, 2014, Invited oral presentation - Symmetry breaking in C. elegans zygote
Fumio Motegi
The Gordon Research Conference on Cell Polarity, 2014, Invited oral presentation
[Invited] - Symmetry breaking in C. elegans zygote
Fumio Motegi
The Manchester U. - MBI joint symposium, 2013, Invited oral presentation
[Invited] - Symmetry breaking: lessons from C. elegans zygote
Fumio Motegi
GCOE Symposium between Kyusyu U and Nat. Univ. Singapore, 2013, Invited oral presentation
[Invited] - Microtubules induce self-organization of polarized PAR domains in Caenorhabditis elegans
Fumio Motegi
第43 回日本細胞生物学会年会 若手最優秀発表選考会, 2010, Invited oral presentation - Microtubules induce self-organization of polarized PAR domains in Caenorhabditis elegans
Fumio Motegi
American Society for Cell Biology annual meeting, 2009, Oral presentation - Microtubules induce self-organization of polarized PAR domains in C. elegans zygotes
Fumio Motegi; Geraldine Seydoux
17th International C. elegans Meeting, 2009, Keynote oral presentation
[Invited] - Dual regulation of cytokinesis by two types of microtubule assembly pathways
Fumio Motegi, Asako Sugimoto
15th International C. elegans Meeting, 2005, Oral presentation - Protein phosphatase 4 is required for chiasma formation during meiosis and fertilization in C. elegans
Fumio Motegi; Asako Sugimoto
East Asia C. elegans Meeting, 2004, Oral presentation - Protein phosphatase 4 is localized to nuclei at the late pachytene stage of meiotic prophase and required for chiasma formation
Fumio Motegi; Asako Sugimoto
14th International C. elegans Meeting, 2003, Oral presentation
- 大学院共通授業科目(一般科目):自然科学・応用科学, 2024年, 修士課程, 大学院共通科目
- 生物化学A(Ⅱ), 2024年, 修士課程, 総合化学院
- 基礎生物化学特論, 2024年, 修士課程, 総合化学院
- 先端総合化学特論Ⅱ, 2024年, 博士後期課程, 総合化学院
- 一般教育演習(フレッシュマンセミナー), 2024年, 学士課程, 全学教育
- Mechanical self-transformation of living systems
Grants-in-Aid for Scientific Research
16 Jun. 2022 - 31 Mar. 2027
茂木 文夫
Japan Society for the Promotion of Science, Grant-in-Aid for Transformative Research Areas (A), 22A302 - Mechanical self-transformation of living systems
Grants-in-Aid for Scientific Research
16 Jun. 2022 - 31 Mar. 2027
茂木 文夫; 柊 卓志; 見学 美根子; 柴田 達夫; 近藤 武史; Phng LiKun; 吉村 成弘
Japan Society for the Promotion of Science, Grant-in-Aid for Transformative Research Areas (A), Hokkaido University, 22H05164 - Self-organization of germ-soma dichotomy by cellular mechano-chemical crosstalk
Grants-in-Aid for Scientific Research
Jun. 2022 - Mar. 2027
茂木 文夫
生物は細胞集団の空間パターンをマクロスケールで秩序化することで、組織・器官としての形と機能を創生する。この細胞集団の秩序化では、それぞれの細胞が機械的力の発生を感知・応答することで細胞内化学シグナル伝達を調節する「力学化学カップリング」を必要とすることが示された。しかしながら、生体内の力作用は直接可視化することができないので、力学化学カップリングの分子機構と生理的役割には未だに不明な点が多い。そこで、生体内の力作用を定量的に評価し、力作用を人為的に操作するための、新規の技術開発が必要とされる。
本研究では先ず、力発生の生理的役割を解明するための技術開発を目的として、マイクロ流体デバイスと光照射による細胞内温度変化を利用して、力発生に関わる標的因子の機能を素早く阻害する「温度遺伝学法」を開発する。この手法では、細胞内局所の温度変化は高速温度感受性の遺伝子変異を導入した細胞骨格因子によって感知され、力発生の局所的変化へと変換される。さらに、紫外域光の照射で細胞内外の微小構造を破壊するマイクロレーザー手術を活用することで、生体内における力発生の局所的な計測・評価・人為的操作を行う。
これらの技術を活用して、線虫胚では多細胞期における非対称分裂を対象に、線虫成体では子宮内における卵母細胞形成を対象として、微小管およびアクチン骨格に由来した力発生が細胞集団と組織の空間パターン秩序化を誘導する機構を解析している。細胞の自律的および非自律的な力学的作用が、細胞集団の自己組織化において極性因子や体細胞・生殖細胞・卵母細胞の運命決定因子に与える影響を定量的に評価することで、マクロスケールの生体秩序化を司る新規原理を解明する。
Japan Society for the Promotion of Science, Grant-in-Aid for Transformative Research Areas (A), Hokkaido University, 22H05165 - 力学作用が制御する卵子の形成と品質管理
研究助成
2024 - 2026
公益財団法人 アステラス病態代謝研究会, Principal investigator - 力学プロセスが駆動する卵子の形成と品質管理
2024年度内藤記念科学研究助成
2024 - 2026
公益財団法人 内藤記念科学振興財団, Principal investigator - 卵母細胞の形成と品質管理を司る「力学刺激−化学反応」連携の解明
2024年度 ビジョナリーリサーチ継続助成(ホップ)
2024 - 2026
公益財団法人 武田科学振興財団, Principal investigator - 細胞内にチューリングパターンは形成可能か?
科学研究費助成事業
30 Jun. 2022 - 31 Mar. 2025
藤原 慶; 茂木 文夫
化学反応と分子拡散の共役(反応拡散共役)によって出現するチューリングパターン(TPs)は、動物の縞模様のように細胞間相互作用で出現する現象を説明可能だが、最新研究において細胞内の分子配置にも重要である証拠が集まってきている。もし細胞の分子配置をTPsが決めていることが証明されれば、分子配置メカニズムにおける生命科学の視点は大きく転換する。そこで本研究では、人工細胞内再構成系と精製された要素を利用し、細胞サイズの空間でTPsが形成可能な条件を解明することを目的としている。
2022年度までに、バクテリアのMin波を改変することでチューリングパターンとみなせる非平衡定常構造の創成に成功した。本成果に関しては2023年度に様々な学会・研究会で成果報告を行った。この成果は、細胞の分子配置をTPsが決めていることの1つの証明となった。また、2023年度は初期胚にみられるTP様の構造であるPAR系の再構成に挑戦した。PARを構成するのに不可欠と考えられている5つの因子を発現精製するために、大腸菌発現、大腸菌抽出液を用いた無細胞転写翻訳系、精製要素からなる無細胞転写翻訳系、小麦胚芽抽出液を用いた無細胞転写翻訳系を試したところ、全長タンパク質の合成可能な条件を発見した。そこで、精製タグの種類や位置、可溶性を検討したところ、1つの要素を除き、発現精製系がほぼ完成した。残された1つに関しては可溶性が著しく低いため、不溶性画分からのリフォールディングや発現条件の最適化を検討する必要が示された。
日本学術振興会, 挑戦的研究(萌芽), 慶應義塾大学, 22K19299 - 光温度遺伝学を活用した生体の自律的パターン形成の解析
科学研究費助成事業
01 Apr. 2022 - 31 Mar. 2025
茂木 文夫
日本学術振興会, 基盤研究(B), 北海道大学, 22H02626 - 微小管メカニクスが誘導する細胞極性パターニング
科学研究費助成事業
07 Oct. 2021 - 31 Mar. 2025
茂木 文夫; 西村 有香子; 木戸秋 悟; 柴田 達夫; 多羅間 充輔
生体内の細胞は、細胞内外に作用する機械的力を利用して、細胞極性の非対称パターンを獲得することが示されたが、この過程で力刺激を感知・応答する分子機構は未だに不明な点が多い。本研究は、細胞骨格である「微小管」のメカニクスを中心とするメカノトランスダクション機構が、細胞極性の非対称パターンを誘導する機構を包括的に理解することを目標とする。
本提案研究では、線虫初期胚とヒト培養細胞を対象とし、細胞内微小管の構造と機能を人為操作する実験手法を確立し、この微小管メカニクスの変動が細胞極性パターンの誘導と維持に及ぼす影響を高解像度ライブイメージングにより解析する。線虫初期胚では、細胞内温度変化によって微小管(チューブリン)、微小管形成中心(中心体)、または微小管モーター(ダイニン複合体)の機能を操作する株を作成し、温度変化と同時にライブイメージングを可能な実験系を確立した。ヒト培養細胞では、メカノトランスダクション構造である細胞接着斑と微小管の相互作用を操作する化学遺伝学手法を確立し、更にこの技術を改変した光遺伝学的手法を開発している。更に、細胞接着斑のメカノトランスダクション機能を操作するために、細胞外基質の機械的性質を微細加工する技術を構築している。今後はこれらの手法を組み合わせて、微小管と細胞外環境のメカニクスを人為操作する技術を確立し、微小管の高速高解像度ライブイメージングと画像解析・数理解析を融合した学際的研究戦略によって、細胞極性化における微小管メカニクスの生理的意義を解明する。
日本学術振興会, 国際共同研究加速基金(国際共同研究強化(B)), 北海道大学, 21KK0127 - 老化による卵子の品質変容における力学作用の機能解析
研究助成
2023 - 2024
第一三共生命科学研究振興財団, Principal investigator - 細胞極性を司る「力学刺激-化学反応」相互作用を理解して人為的に操作する
ビジョナリーリサーチ助成
2021 - 2023
公益財団法⼈武⽥科学振興財団, Principal investigator - 細胞極性の欠損を理解して制御する
研究助成金
2021 - 2023
公益財団法人東レ科学振興会, Principal investigator - 国際学術集会「Mechanical control of cell and tissue self-organization」
令和6年度前半期 海外招聘補助金
2023
公益財団法人中外創薬科学財団, Principal investigator - 国際学術集会「Mechanical control of cell and tissue self-organization」
学術集会および科学技術振興事業助成
2023
公益財団法人セコム科学技術振興財団, Principal investigator - 国際学術集会「Mechanical control of cell and tissue self-organization」
海外学者招聘助成金
2023
公益財団法人 中谷医工計測技術振興財団, Principal investigator - 国際学術集会「Mechanical control of cell and tissue self-organization」
国際シンポジウム開催助成⾦
2023
公益財団法人 上原記念生命科学財団, Principal investigator - 国際学術集会「Mechanical control of cell and tissue self-organization」
第55回(2023年度)内藤記念海外学者招聘助成金(前期)
2023
公益財団法人 内藤記念科学振興財団, Principal investigator - International symposium on mechanical control of cell and tissue selforganization
Scientific Meeting Grant Agreement
2023
THE COMPANY OF BIOLOGISTS LIMITED, Principal investigator - 第61回日本生物物理学会年会シンポジウム
海外招聘者旅費助成
2023
公益財団法人 中谷医工計測技術振興財団, Principal investigator - 細胞極性の破綻を抑制する新規遺伝学的機構の解明
自然科学研究助成
2022
公益財団法人三菱財団, Principal investigator - 新規の光温度遺伝学技術で探求する生体自律化メカニクス
研究奨励金
2022
公益財団法人ノバルティス科学振興財団, Principal investigator - 線虫C. elegans を用いた老化・代謝変化に応答した極性輸送機構の解析
内分泌・代謝学共同研究拠点共同研究
2021
群馬大学生体調節研究所, Principal investigator - 「細胞極性の欠損が引き起こす組織破綻」を理解して抑制する
研究助成金
2021
公益財団法人寿原記念財団, Principal investigator - 光温度遺伝学法による生体内力発生の機能解析
技術開発研究助成
2021
公益財団法人 中谷医工計測技術振興財団, Principal investigator - 光温度遺伝学を活用した生体の自律的パターン形成の解析
2021
一般財団法人 北海道B型肝炎訴訟オレンジ基金, Principal investigator - 線虫C. elegans を用いた老化・代謝変化に応答した極性輸送機構の解析
内分泌・代謝学共同研究拠点共同研究
2020
群馬大学生体調節研究所, Principal investigator - PAR-1/4が誘導する細胞-組織極性の制御機構
研究助成金
2020
公益財団法人アステラス病態代謝研究会, Principal investigator - 「細胞極性の欠損による疾患発症」を理解して抑制する
研究助成金
2020
公益財団法人上原記念生命科学財団, Principal investigator - 温度遺伝学で探求する非対称分裂メカニクス
研究助成金
2020
公益財団法人住友財団, Principal investigator - 受精卵に細胞極性を誘導する分子メカニズムの全容を解明する
成茂動物科学振興基金
2020
公益信託 成茂動物科学振興基金, Principal investigator - New Optical System to Visualize Cellular Self-organization
日本・シンガポール 二国間共同研究プログラム
2015 - 2018
A-Star Singapore, Principal investigator, 1514324022 - The Mechanisms of Breaking Cellular Symmetry in Metazoan Development
NRF Fellowship
Aug. 2012 - Jul. 2017
National Research Foundation Singapore, Principal investigator, Competitive research funding, NRF-NRFF2012-08 - 体系的RNAi法を利用した線虫C.elegansにおける微小管制御因子の解析
科学研究費助成事業
2003 - 2004
茂木 文夫
微小管は主にセントロソームで形成され、分裂期にはその構造をダイナミックに変化させるが、微小管のダイナミクスを調節する機構および微小管による細胞分裂の制御機構については未だ理解が進んでいない。RNA干渉法を用いて線虫初期胚の微小管形成にはたらく因子を探索した結果、セントロソームに局在することが知られているγ-tubulin (TBG-1)およびaurora kinase A (AIR-1)は、セントロソームにおける微小管形成に並列に寄与していることを明らかにした。さらに、TBG-1依存的な微小管とAIR-1依存的な微小管では細胞表層の収縮へのはたらきかけが異なることが示された。TBG-1欠損胚でみられるAIR-1依存的な微小管は、細胞表層へと到達した後にも伸長を続け、anaphase後期にみられる細胞表層の収縮を抑制した。一方、AIR-1欠損胚でみられるTBG-1依存的な微小管は、細胞表層に到達すると短縮・伸長を繰り返し、anaphase初期に細胞表層の収縮を促進した。このことから、TBG-1とAIR-1は、セントロソームにおける微小管形成を介して、細胞表層の収縮に対して相反する役割を示すことが示唆された。つぎに、野生型初期胚の微小管動態の観察を行った結果、anaphase初期の分裂面周辺の細胞表層にはTBG-1依存的微小管と類似した短縮・伸長を繰り返す微小管が集積していたのに対して、anaphase後期には分裂面以外の細胞表層に伸長を続けるAIR-1依存的微小管と類似した微小管が観察された。以上の結果から、細胞質分裂における細胞表層の収縮性制御には、TBG-1およびAIR-1が関与する二つの独立の微小管制御機構が働いている可能性が考えられる。
日本学術振興会, 若手研究(B), 独立行政法人理化学研究所, 15770115
