Fumio Motegi

fumio-portraitPrincipal Investigator, MBI

email: fmotegi@tll.org.sg

Principal Investigator, MBI and Temasek Lifesciences Laboratory,
Assistant Professor, Dept of Biological Sciences, NUS,
NRF Fellow

Mechanobiology of 1) cell polarity establishment and 2) soma-germline fate determination

Cell polarity, establishment of spatial asymmetry within a cell, is necessary for diverse processes in living organisms. Dedicated polarity proteins generate and maintain cellular asymmetry, leading to establishment of functional architecture in many types of cells. Despite the conserved role of polarity proteins, a fundamental question remains unanswered: How do developmental cues break cellular symmetry along the body axis during embryogenesis?

Our group is interested in understanding the mechanics of 1) initiation of cell polarization and 2) spatial patterning of cellular asymmetry. A simple model system, C. elegans zygote, provides the unique opportunity to explore such initial procedures in cell polarization, as the zygotes do not rely on pre-localized proteins/RNAs or extrinsic cues to trigger asymmetry but instead undergo “de novo” polarization (Movie 1). By taking multi-disciplinary approach with genetics, biochemistry, and modern imaging technology, our group aims at

1. Defining the nature of the cue that initiates polarization
2. Assessing the mechanics of spatial patterning of cellular asymmetry
3. Understanding the role of polarity kinases in germ-soma dichotomy

These views will delve into the basic principles of cell polarity and yield insights into how a developing embryo commits to somatic or germline cell fates with precision and accuracy. The molecular similarity of C. elegans to other systems makes it very likely that this project will highlight highly conserved mechanisms and lead to insights into asymmetric division in stem cells, prevention of cancer, and tissue regeneration.

Movie 1: Breaking symmetry of embryonic polarity

Symmetry breaking is the process by which cellular uniformity is broken to generate asymmetry in space. The cue that triggers symmetry breaking leads to the modulation of cell cortex to generate two distinct domains. The C. elegans zygote becomes polarized after fertilization by generating distinct domains: the anterior domain contains a complex of PAR-3, PAR-6, and atypical protein kinase C/aPKC (shown in magenta), and the posterior domain includes PAR-1 kinase and the RING protein PAR-2 (shown in green). Segregation of two sets of PAR proteins is critical for decision whether to become somatic cells or germ cells.

Fumio Motegi obtained his university diploma at Tokyo University of Science and completed his Master’s study and doctoral degree at the University of Tokyo. He did his postdoctoral work with Prof. Asako Sugimoto at RIKEN Center for Developmental Biology and with Prof. Geraldine Seydoux at Johns Hopkins University. He joined MBI and Temasek Lifesciences Laboratory as a Principal Investigator in August 2012 and holds a joint appointment as an Assistant Professor at Department of Biological Sciences at National University of Singapore.

Motegi F, Seydoux, G. (2013) The PAR network: redundancy and robustness in a symmetry-breaking system. Philosophical Transactions of the Royal Society B (invited review article)

Motegi F, Zonies S, Hao Y, Cuenca A, Griffin E, Seydoux G. (2011) Microtubules induce self-organization of polarized PAR domains in Caenohrabditis elegans zygotes. Nat. Cell Biol 13: 1361-1367 Highlighted in Previews of Developmental Cell (21; 981-982 (2011)) and Nature Reviews in Molecular Cell Biology (12; 693 (2011)), selected by Faculty of 1000

Zonies S, Motegi F, Hao Y, Seydoux G. (2010) Symmetry breaking and polarization of the C. elegans zygote by the polarity protein PAR-2. Development 137(10): 1669-77 Selected by Faculty of 1000

Terasawa M, Toya M, Motegi F, Mana M, Nakamura K, Sugimoto A. (2010) 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. Genes to Cells 15(11): 1145-5

Gallo CM, Wang JT, Motegi F, Seydoux G. (2010) Cytoplasmic Partitioning of P Granule Components Is Not Required to Specify the Germline in C. elegans. Science 330: 1685-168 Highlighted in Current Biology (21; R155-157 (2011)), selected by Faculty of 1000

Gassmann R, Essex A, Hu JS, Maddox PS, Motegi F, Sugimoto A, O’Rourke SM, Bowerman B, McLeod I, Yates JR, Oegema K, Cheeseman IM, Desai A. (2008) A new mechanism controlling kinetochore-microtubule interactions revealed by comparison of two dynein-targeting components: SPDL-1 and the Rod/Zwilich/ZW10. Genes and Development 22: 2385-2399

Motegi F, Seydoux G. (2007) Revisiting the role of microtubules in C. elegans polarity. J. Cell Biol 179: 367-369

Motegi F, Sugimoto A. (2006) Sequential function of RHO-1 and CDC-42 establishes cell polarity in Caenohrabditis elegans embryos. Nat. Cell Biol 8: 978-985 Selected in “A decade of Nature Cell Biology” papers, Highlighted in Development (134: 1035-1043 (2007)), selected by Faculty of 1000

Motegi F, Veralde N, Piano F, Sugimoto A. (2006) Two phases of astral microtubule activity during cytokinesis in C. elegans embryos. Dev. Cell 10: 509-520 Selected by Faculty of 1000