Updated on 2022/10/26

写真a

 
SHINODA Tomoyasu
 
Organization
Graduate School of Medicine Program in Integrated Medicine Anatomy and Cell Biology Assistant Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine
Title
Assistant Professor

Degree 1

  1. 博士(理学) ( 2006.1   名古屋大学 ) 

Research Interests 1

  1. brain development

Research Areas 2

  1. Life Science / Developmental biology

  2. Life Science / Developmental biology

Current Research Project and SDGs 1

  1. 脳発生の定量的解析

Research History 6

  1. Nagoya University   Graduate School of Medicine Program in Integrated Medicine Anatomy and Cell Biology   Assistant Professor

    2013.4

  2. Nagoya University   Graduate School of Medicine Program in Integrated Medicine Anatomy and Cell Biology   Assistant Professor

    2014.4

  3. Nagoya University   Graduate School of Medicine Program in Integrated Medicine Anatomy and Cell Biology   Designated assistant professor

    2013.4 - 2014.3

  4. Nagoya University   Department of anatomy and cell biology, Graduate school of medicine   Designated assistant professor

    2012.4 - 2013.3

  5. Nagoya University   Department of anatomy and cell biology, Graduate school of medicine   Researcher

    2011.9 - 2012.3

  6. Aichi human service center   Researcher

    2008.2 - 2011.1

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    Country:Japan

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Education 3

  1. Nagoya University   Graduate School, Division of Natural Science

    - 2005.3

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    Country: Japan

  2. Nagoya University   Graduate School, Division of Natural Science

    - 2005.3

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    Country: Japan

  3. Nagoya University   Graduate School, Division of Natural Science

    - 2005.3

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    Country: Japan

Professional Memberships 8

  1. 日本解剖学会

  2. 日本発生生物学会

  3. 日本神経科学会

  4. 日本細胞生物学会

  5. 日本解剖学会

  6. 日本細胞生物学会

  7. 日本神経科学会

  8. 日本発生生物学会

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Awards 1

  1. BP/NP/NC 2006 Nagoya outostanding paper award

    2006.9   Joint meeting of the 27th annual meeting of the Japanese Society of Biological Psychiatry, 35th annual meeting of the Japanese Society of neuropsychopharmacology, 49th annual meeting of the Japanese Society for neurochemistry   DISC1 regulates the localization of Grb2 via Kinesin-1

    Tomoyasu Shinoda

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

 

Papers 38

  1. Two-photon microscopic observation of cell-production dynamics in the developing mammalian neocortex in utero Reviewed

    Kawasoe Ryotaro, Shinoda Tomoyasu, Hattori Yuki, Nakagawa Mami, Pham Trung Quang, Tanaka Yoshihiro, Sagou Ken, Saito Kanako, Katsuki Satoru, Kotani Tomomi, Sano Akihito, Fujimori Toshihiko, Miyata Takaki

    DEVELOPMENT GROWTH & DIFFERENTIATION   Vol. 62 ( 2 ) page: 118 - 128   2020.2

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Development Growth and Differentiation  

    Morphogenesis and organ development should be understood based on a thorough description of cellular dynamics. Recent studies have explored the dynamic behaviors of mammalian neural progenitor cells (NPCs) using slice cultures in which three-dimensional systems conserve in vivo-like environments to a considerable degree. However, live observation of NPCs existing truly in vivo, as has long been performed for zebrafish NPCs, has yet to be established in mammals. Here, we performed intravital two-photon microscopic observation of NPCs in the developing cerebral cortex of H2B-EGFP or Fucci transgenic mice in utero. Fetuses in the uterine sac were immobilized using several devices and were observed through a window made in the uterine wall and the amniotic membrane while monitoring blood circulation. Clear visibility was obtained to the level of 300 μm from the scalp surface of the fetus, which enabled us to quantitatively assess NPC behaviors, such as division and interkinetic nuclear migration, within a neuroepithelial structure called the ventricular zone at embryonic day (E) 13 and E14. In fetuses undergoing healthy monitoring in utero for 60 min, the frequency of mitoses observed at the apical surface was similar to those observed in slice cultures and in freshly fixed in vivo specimens. Although the rate and duration of successful in utero observations are still limited (33% for ≥10 min and 14% for 60 min), further improvements based on this study will facilitate future understanding of how organogenetic cellular behaviors occur or are pathologically influenced by the systemic maternal condition and/or maternal-fetal relationships.

    DOI: 10.1111/dgd.12648

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  2. Neural stem cells use external forces to streamline collective nuclear migration and secure cytogenesis Reviewed

    Shinoda Tomoyasu, Kawaue Takumi, Miyata Takaki

      Vol. 90 ( 6 ) page: 820 - 824   2018.12

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  3. Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics Reviewed

    Mingyue Jin, Oz Pomp, Tomoyasu Shinoda, Shiori Toba, Takayuki Torisawa, Ken'ya Furuta, Kazuhiro Oiwa, Takuo Yasunaga, Daiju Kitagawa, Shigeru Matsumura, Takaki Miyata, Thong Teck Tan, Bruno Reversade, Shinji Hirotsune

    SCIENTIFIC REPORTS   Vol. 7   page: 39902   2017.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    Human mutations in KATNB1 (p80) cause severe congenital cortical malformations, which encompass the clinical features of both microcephaly and lissencephaly. Although p80 plays critical roles during brain development, the underlying mechanisms remain predominately unknown. Here, we demonstrate that p80 regulates microtubule (MT) remodeling in combination with NuMA (nuclear mitotic apparatus protein) and cytoplasmic dynein. We show that p80 shuttles between the nucleus and spindle pole in synchrony with the cell cycle. Interestingly, this striking feature is shared with NuMA. Importantly, p80 is essential for aster formation and maintenance in vitro. siRNA-mediated depletion of p80 and/or NuMA induced abnormal mitotic phenotypes in cultured mouse embryonic fibroblasts and aberrant neurogenesis and neuronal migration in the mouse embryonic brain. Importantly, these results were confirmed in p80-mutant harboring patient-derived induced pluripotent stem cells and brain organoids. Taken together, our findings provide valuable insights into the pathogenesis of severe microlissencephaly, in which p80 and NuMA delineate a common pathway for neurogenesis and neuronal migration via MT organization at the centrosome/spindle pole.

    DOI: 10.1038/srep39902

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  4. Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity Reviewed

    Daisuke Tsuboi, Keisuke Kuroda, Motoki Tanaka, Takashi Namba, Yukihiko Iizuka, Shinichiro Taya, Tomoyasu Shinoda, Takao Hikita, Shinsuke Muraoka, Michiro Iizuka, Ai Nimura, Akira Mizoguchi, Nobuyuki Shiina, Masahiro Sokabe, Hideyuki Okano, Katsuhiko Mikoshiba, Kozo Kaibuchi

    NATURE NEUROSCIENCE   Vol. 18 ( 5 ) page: 698 - 707   2015.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    Disrupted-in-schizophrenia 1 (DISC1) is a susceptibility gene for major psychiatric disorders, including schizophrenia. DISC1 has been implicated in neurodevelopment in relation to scaffolding signal complexes. Here we used proteomic analysis to screen for DISC1 interactors and identified several RNA-binding proteins, such as hematopoietic zinc finger (HZF), that act as components of RNA-transporting granules. HZF participates in the mRNA localization of inositol-1,4,5-trisphosphate receptor type 1 (ITPR1), which plays a key role in synaptic plasticity. DISC1 colocalizes with HZF and ITPR1 mRNA in hippocampal dendrites and directly associates with neuronal mRNAs, including ITPR1 mRNA. The binding potential of DISC1 for ITPR1 mRNA is facilitated by HZF. Studies of Disc1-knockout mice have revealed that DISC1 regulates the dendritic transport of Itpr1 mRNA by directly interacting with its mRNA. The DISC1-mediated mRNA regulation is involved in synaptic plasticity. We show that DISC1 binds ITPR1 mRNA with HZF, thereby regulating its dendritic transport for synaptic plasticity.

    DOI: 10.1038/nn.3984

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  5. Dysbindin-1, a schizophrenia-related molecule, is involved in the regulation of neuronal dendritic development

    Ito H., Morishita R., Shinoda T., Iwamoto I., Sudo K., Okamoto K., Nagata K.

    Molecular Psychiatry   Vol. 15 ( 10 )   2010.10

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    Language:Japanese   Publisher:Molecular Psychiatry  

    DOI: 10.1038/mp.2010.93

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  6. Proteomics analysis of susceptibility genes for schizophrenia

    Taya Shinichiro, Tsuboi Daisuke, Shinoda Tomoyasu, Kaibuchi Kozo

    Abstracts for Annual Meeting of Japanese Proteomics Society   Vol. 2007 ( 0 ) page: 53 - 53   2007

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    Language:Japanese   Publisher:Japanese Proteomics Society (Japan Human Proteome Organisation)  

    DOI: 10.14889/jhupo.2007.0.53.0

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  7. Two-photon microscopic observation of cell-production dynamics in the developing mammalian neocortex in utero. Reviewed

    Kawasoe R, Shinoda T, Hattori Y, Nakagawa M, Pham TQ, Tanaka Y, Sagou K, Saito K, Katsuki S, Kotani T, Sano A, Fujimori T, Miyata T

    Development, Growth and Differentiation   Vol. 62 ( 2 ) page: 118 - 128   2020.1

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    Publishing type:Research paper (scientific journal)  

  8. Dorsal-to-Ventral Cortical Expansion Is Physically Primed by Ventral Streaming of Early Embryonic Preplate Neurons. International journal

    Kanako Saito, Mayumi Okamoto, Yuto Watanabe, Namiko Noguchi, Arata Nagasaka, Yuta Nishina, Tomoyasu Shinoda, Akira Sakakibara, Takaki Miyata

    Cell reports   Vol. 29 ( 6 ) page: 1555 - +   2019.11

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    Despite recent studies elucidating the molecular mechanisms underlying cortical patterning and map formation, very little is known about how the embryonic pallium expands ventrally to form the future cortex and the nature of the underlying force-generating events. We find that neurons born at embryonic day 10 (E10) in the mouse dorsal pallium ventrally stream until E13, thereby superficially spreading the preplate, and then constitute the subplate from E14. From E11 to E12, the preplate neurons migrate, exerting pulling and pushing forces at the process and the soma, respectively. At E13, they are morphologically heterogeneous, with ∼40% possessing corticofugal axons, which are found to be in tension. Ablation of these E10-born neurons attenuates both deflection of radial glial fibers (by E13) and extension of the cortical plate (by E14), which should occur ventrally, and subsequently shrinks the postnatal neocortical map dorsally. Thus, the preplate stream physically primes neocortical expansion and arealization.

    DOI: 10.1016/j.celrep.2019.09.075

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  9. Lzts1 controls both neuronal delamination and outer radial glial-like cell generation during mammalian cerebral development. Reviewed International journal

    Kawaue T, Shitamukai A, Nagasaka A, Tsunekawa Y, Shinoda T, Saito K, Terada R, Bilgic M, Miyata T, Matsuzaki F, Kawaguchi A

    Nature Communications   Vol. 10 ( 1 ) page: 2780 - 2780   2019.6

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    In the developing central nervous system, cell departure from the apical surface is the initial and fundamental step to form the 3D, organized architecture. Both delamination of differentiating cells and repositioning of progenitors to generate outer radial glial cells (oRGs) contribute to mammalian neocortical expansion; however, a comprehensive understanding of their mechanisms is lacking. Here, we demonstrate that Lzts1, a molecule associated with microtubule components, promotes both cell departure events. In neuronally committed cells, Lzts1 functions in apical delamination by altering apical junctional organization. In apical RGs (aRGs), Lzts1 expression is variable, depending on Hes1 expression levels. According to its differential levels, Lzts1 induces diverse RG behaviors: planar division, oblique divisions of aRGs that generate oRGs, and their mitotic somal translocation. Loss-of-function of lzts1 impairs all these cell departure processes. Thus, Lzts1 functions as a master modulator of cellular dynamics, contributing to increasing complexity of the cerebral architecture during evolution.

    DOI: 10.1038/s41467-019-10730-y

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  10. Elasticity-based boosting of neuroepithelial nucleokinesis via indirect energy transfer from mother to daughter

    Shinoda Tomoyasu, Nagasaka Arata, Inoue Yasuhiro, Higuchi Ryo, Minami Yoshiaki, Kato Kagayaki, Suzuki Makoto, Kondo Takefumi, Kawaue Takumi, Saito Kanako, Ueno Naoto, Fukazawa Yugo, Nagayama Masaharu, Miura Takashi, Adachi Taiji, Miyata Takaki

    PLOS BIOLOGY   Vol. 16 ( 4 )   2018.4

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    DOI: 10.1371/jourrnal.pbio.2004426

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  11. Elasticity-based boosting of neuroepithelial nucleokinesis via indirect energy transfer from mother to daughter.

    Shinoda T, Nagasaka A, Inoue Y, Higuchi R, Minami Y, Kato K, Suzuki M, Kondo T, Kawaue T, Saito K, Ueno N, Fukazawa Y, Nagayama M, Miura T, Adachi T, Miyata T

    PLoS biology   Vol. 16 ( 4 ) page: e2004426   2018.4

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    DOI: 10.1371/journal.pbio.2004426

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  12. Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics. Reviewed

    Jin M, Pomp O, Shinoda T, Toba S, Torisawa T, Furuta K, Oiwa K, Yasunaga T, Kitagawa D, Matsumura S, Miyata T, Tan TT, Reversade B, Hirotsune S.

    Scientific reports   Vol. 7   page: 39902   2017.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/srep39902.

  13. Synergistic action of nectins and cadherins generates the mosaic cellular pattern of the olfactory epithelium. Reviewed

    Katsunuma S, Honda H, Shinoda T, Ishimoto Y, Miyata T, Kiyonari H, Abe T, Nibu K, Takai Y, Togashi H.

    J Cell Biol   Vol. 212   page: 561-575   2016.2

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    DOI: 561-575

  14. Synergistic action of nectins and cadherins generates the mosaic cellular pattern of the olfactory epithelium Reviewed

    Sayaka Katsunuma, Hisao Honda, Tomoyasu Shinoda, Yukitaka Ishimoto, Takaki Miyata, Hiroshi Kiyonari, Takaya Abe, Ken-ichi Nibu, Yoshimi Takai, Hideru Togashi

    JOURNAL OF CELL BIOLOGY   Vol. 212 ( 5 ) page: 561 - 575   2016.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ROCKEFELLER UNIV PRESS  

    In the olfactory epithelium (OE), olfactory cells (OCs) and supporting cells (SCs), which express different cadherins, are arranged in a characteristic mosaic pattern in which OCs are enclosed by SCs. However, the mechanism underlying this cellular patterning is unclear. Here, we show that the cellular pattern of the OE is established by cellular rearrangements during development. In the OE, OCs express nectin-2 and N-cadherin, and SCs express nectin-2, nectin-3, E-cadherin, and N-cadherin. Heterophilic trans-interaction between nectin-2 on OCs and nectin-3 on SCs preferentially recruits cadherin via a-catenin to heterotypic junctions, and the differential distributions of cadherins between junctions promote cellular intercalations, resulting in the formation of the mosaic pattern. These observations are confirmed by model cell systems, and various cellular patterns are generated by the combinatorial expression of nectins and cadherins. Collectively, the synergistic action of nectins and cadherins generates mosaic pattern, which cannot be achieved by a single mechanism.

    DOI: 10.1083/jcb.201509020

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  15. Differences in the Mechanical Properties of the Developing Cerebral Cortical Proliferative Zone between Mice and Ferrets at both the Tissue and Single-Cell Levels. Reviewed

    Nagasaka A, Shinoda T, Kawaue T, Suzuki M, Nagayama K, Matsumoto T, Ueno N, Kawaguchi A, Miyata T

    Frontiers in cell and developmental biology   Vol. 4 ( NOV ) page: 139   2016

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    DOI: 10.3389/fcell.2016.00139

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  16. Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity. Reviewed

    Tsuboi D, Kuroda K, Tanaka M, Namba T, Iizuka Y, Taya S, Shinoda T, Hikita T, Muraoka S, Iizuka M, Nimura A, Mizoguchi A, Shiina N, Sokabe M, Okano H, Mikoshiba K, Kaibuchi K.

    Nat Neurosci.   ( 18 ) page: 698-707   2015.5

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    DOI: 10.1038/nn.3984.

  17. Interkinetic nuclear migration generates and opposes ventricular-zone crowding: insight into tissue mechanics. Reviewed

    Miyata T, Okamoto M, Shinoda T, Kawaguchi A

    Front Cell Neurosci.   Vol. 8 ( 8 ) page: 473   2015.1

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.3389/fncel.2014.00473

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  18. Ferret-mouse differences in interkinetic nuclear migration and cellular densification in the neocortical ventricular zone Reviewed

    Okamoto Mayumi, Shinoda Tomoyasu, Kawaue Takumi, Nagasaka Arata, Miyata Takaki

    NEUROSCIENCE RESEARCH   Vol. 86   page: 88 - 95   2014.9

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    Publishing type:Research paper (scientific journal)   Publisher:Neuroscience Research  

    DOI: 10.1016/j.neures.2014.10.006

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  19. Neurogenin2-d4Venus and Gadd45g-d4Venus transgenic mice: visualizing mitotic and migratory behaviors of cells committed to the neuronal lineage in the developing mammalian brain. Reviewed

    Kawaue T, Sagou K, Kiyonari H, Ota K, Okamoto M, Shinoda T, Kawaguchi A, Miyata T.

    Dev Growth Differ.   ( 56 ) page: 293-304   2014.5

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/dgd.12131.

  20. Ferret-mouse differences in interkinetic nuclear migration and cellular densification in the neocortical ventricular zone. Reviewed

    Okamoto M, Shinoda T, Kawaue T, Nagasaka A, Miyata T.

    Neurosci Res.     page: 88-95   2014

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  21. TAG-1-assisted progenitor elongation streamlines nuclear migration to optimize subapical crowding. Reviewed

    Okamoto M, Namba T, Shinoda T, Kondo T, Watanabe T, Inoue Y, Takeuchi K, Enomoto Y, Ota K, Oda K, Wada Y, Sagou K, Saito K, Sakakibara A, Kawaguchi A, Nakajima K, Adachi T, Fujimori T, Ueda M, Hayashi S, Kaibuchi K, Miyata T.

    Nat Neurosci.   ( 16 ) page: 1556-1566   2013.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nn.3525.

  22. Application of in utero electroporation and live imaging in the analyses of neuronal migration during mouse brain development Reviewed

    Yoshiaki V. Nishimura, Tomoyasu Shinoda, Yutaka Inaguma, Hidenori Ito, Koh-ichi Nagata

    MEDICAL MOLECULAR MORPHOLOGY   Vol. 45 ( 1 ) page: 1 - 6   2012.3

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    Publishing type:Research paper (scientific journal)   Publisher:SPRINGER JAPAN KK  

    Correct neuronal migration is crucial for brain architecture and function. During cerebral cortex development (corticogenesis), excitatory neurons generated in the proliferative zone of the dorsal telencephalon (mainly ventricular zone) move through the intermediate zone and migrate past the neurons previously located in the cortical plate and come to rest just beneath the marginal zone. The in utero electroporation technique is a powerful method for rapid gain-and loss-of-function studies of neuronal development, especially neuronal migration. This method enabled us to introduce genes of interest into ventricular zone progenitor cells of mouse embryos and to observe resulting phenotypes such as proliferation, migration, and cell morphology at later stages. In this Award Lecture Review, we focus on the application of the in utero electroporation method to functional analyses of cytoskeleton-related protein septin. We then refer to, as an advanced technique, the in utero electroporation-based real-time imaging method for analyses of cell signaling regulating neuronal migration. The in utero electroporation method and its application would contribute to medical molecular morphology through identification and characterization of the signaling pathways disorganized in various neurological and psychiatric disorders.

    DOI: 10.1007/s00795-011-0557-0

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  23. ROLE OF THE SEPTIN IN NEURAL CELL MIGRATION DURING BRAIN DEVELOPMENT Reviewed

    Nagata K., Shinoda T., Nishimura Y. V, Ito H.

    JOURNAL OF NEUROCHEMISTRY   Vol. 118   page: 169 - 169   2011.8

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  24. Functional analysis of Dysbindin, a schizophrenia risk factor, in dendritic spine formation Reviewed

    Ito H., Morishita R., Nishimura Y., Shinoda T., Iwamoto I., Nagata K-I.

    MOLECULAR BIOLOGY OF THE CELL   Vol. 22   2011

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  25. SCHIZOPHRENIA SUSCEPTIBILITY GENE, DYSBINDIN-1, REGULATES THE DENDRITIC SPINE FORMATION: EVIDENCE SUPPORTING NEURODEVELOPMENTAL HYPOTHESIS Reviewed

    Ito H., Morishita R., Shinoda T., Iwamoto I., Sudo K., Nagata K.

    JOURNAL OF NEUROCHEMISTRY   Vol. 115   page: 15 - 15   2010.10

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  26. Possible roles of septins in the SNARE complex formation

      Vol. 61 ( 3 ) page: 242 - 246   2010.6

  27. Septin 14 Is Involved in Cortical Neuronal Migration via Interaction with Septin 4 Reviewed

    Tomoyasu Shinoda, Hidenori Ito, Kaori Sudo, Ikuko Iwamoto, Rika Morishita, Koh-ichi Nagata

    MOLECULAR BIOLOGY OF THE CELL   Vol. 21 ( 8 ) page: 1324 - 34   2010.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER SOC CELL BIOLOGY  

    Septins are a family of conserved guanosine triphosphate/guanosine diphosphate-binding proteins implicated in a variety of cellular functions such as cell cycle control and cytokinesis. Although several members of septin family, including Septin 14 (Sept14), are abundantly expressed in nervous tissues, little is known about their physiological functions, especially in neuronal development. Here, we report that Sept14 is strongly expressed in the cortical plate of developing cerebral cortex. Knockdown experiments by using the method of in utero electroporation showed that reduction of Sept14 caused inhibition of cortical neuronal migration. Whereas cDNA encoding RNA interference-resistant Sept14 rescued the migration defect, the C-terminal deletion mutant of Sept14 did not. Biochemical analyses revealed that C-terminal coiled-coil region of Sept14 interacts with Septin 4 (Sept4). Knockdown experiments showed that Sept4 is also involved in cortical neuronal migration in vivo. In addition, knockdown of Sept14 or Sept4 inhibited leading process formation in migrating cortical neurons. These results suggest that Sept14 is involved in neuronal migration in cerebral cortex via interaction with Sept4.

    DOI: 10.1091/mbc.e09-10-0869

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  28. Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation Reviewed

    Ito Hidenori, Morishita Rika, Shinoda Tomoyasu, Sudo Kaori, Iwamoto Ikuko, Nagata Koh-ichi

    NEUROSCIENCE RESEARCH   Vol. 68   page: E120 - E120   2010

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    DOI: 10.1016/j.neures.2010.07.2101

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  29. Septin 14 is involved in cortical neuronal migration via interaction with Septin 4 Reviewed

    Tomoyasu Shinoda, Hidenori Ito, Kaori Sudo, Ikuko Iwamoto, Rika Morishita, Koh-ichi Nagata

    NEUROSCIENCE RESEARCH   Vol. 68   page: E251 - E251   2010

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2010.07.1113

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  30. Proteomic analysis reveals novel binding partners of dysbindin, a schizophrenia-related protein Reviewed

    Takao Hikita, Shinichiro Taya, Yasutaka Fujino, Setsuko Taneichi-Kuroda, Kanae Ohta, Daisuke Tsuboi, Tomoyasu Shinoda, Keisuke Kuroda, Yusuke Funahashi, Junko Uraguchi-Asaki, Ryota Hashimoto, Kozo Kaibuchi

    JOURNAL OF NEUROCHEMISTRY   Vol. 110 ( 5 ) page: 1567 - 1574   2009.9

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL PUBLISHING, INC  

    Schizophrenia is a complex mental disorder with fairly high level of heritability. Dystrobrevin binding protein 1, a gene encoding dysbindin protein, is a susceptibility gene for schizophrenia that was identified by family-based association analysis. Recent studies revealed that dysbindin is involved in the exocytosis and/or formation of synaptic vesicles. However, the molecular function of dysbindin in synaptic transmission is largely unknown. To investigate the signaling pathway in which dysbindin is involved, we isolated dysbindin-interacting molecules from rat brain lysate by combining ammonium sulfate precipitation and dysbindin-affinity column chromatography, and identified dysbindin-interacting proteins by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and liquid chromatography-tandem mass spectrometry. Proteins involved in protein localization process, including Munc18-1, were identified as dysbindininteracting proteins. Munc18-1 was co-immunoprecipitated with dysbindin from rat brain lysate, and directly interacted with dysbindin in vitro. In primary cultured rat hippocampal neurons, a part of dysbindin was co-localized with Munc18-1 at pre-synaptic terminals. Our result suggests a role for dysbindin in synaptic vesicle exocytosis via interaction with Munc18-1.

    DOI: 10.1111/j.1471-4159.2009.06257.x

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  31. Sept14 is involved in the proper positioning of cortical pyramidal neuron Reviewed

    Tomoyasu Shinoda, Hidenori Ito, Kaori Sudo, Ikuko Iwamoto, Rika Morishita, Koh-Ichi Nagata

    NEUROSCIENCE RESEARCH   Vol. 65   page: S94 - S94   2009

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2009.09.395

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  32. DISC1 regulates neurotrophin-induced axon elongation via interaction with Grb2 Reviewed

    Tomoyasu Shinoda, Shinichiro Taya, Daisuke Tsuboi, Takao Hikita, Reiko Matsuzawa, Setsuko Kuroda, Akihiro Iwamatsu, Kozo Kaibuchi

    JOURNAL OF NEUROSCIENCE   Vol. 27 ( 1 ) page: 4 - 14   2007.1

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:SOC NEUROSCIENCE  

    Disrupted-in-Schizophrenia-1 (DISC1) is a candidate gene for susceptibility of schizophrenia. In the accompanying paper (Taya et al., 2006), we report that DISC1 acts as a linker between Kinesin-1 and DISC1-interacting molecules, such as NudE-like, lissencephaly-1, and 14-3-3 epsilon. Here we identified growth factor receptor bound protein 2 (Grb2) as a novel DISC1-interacting molecule. Grb2 acts as an adaptor molecule that links receptor tyrosine kinases and the Ras-extracellular signal-regulated kinase (ERK) pathway. DISC1 formed a ternary complex with Grb2 and kinesin heavy chain KIF5A of Kinesin-1. In cultured rat hippocampal neurons, both DISC1 and Grb2 partially colocalized at the distal part of axons. Knockdown of DISC1 or kinesin light chains of Kinesin-1 by RNA interference inhibited the accumulation of Grb2 from the distal part of axons. Knockdown of DISC1 also inhibited the neurotrophin-3 (NT-3)-induced phosphorylation of ERK-1/2 at the distal part of axons and inhibited NT-3-induced axon elongation. These results suggest that DISC1 is required for NT-3-induced axon elongation and ERK activation at the distal part of axons by recruiting Grb2 to axonal tips.

    DOI: 10.1523/JNEUROSCI.3825-06.2007

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  33. DISC1 regulates the transport of the NUDEL/LIS1/14-3-3 epsilon complex through Kinesin-1 Reviewed

    Shinichiro Taya, Tomoyasu Shinoda, Daisuke Tsuboi, Junko Asaki, Kumiko Nagai, Takao Hikita, Setsuko Kuroda, Keisuke Kuroda, Mariko Shimizu, Shinji Hirotsune, Akihiro Iwamatsu, Kozo Kaibuchi

    JOURNAL OF NEUROSCIENCE   Vol. 27 ( 1 ) page: 15 - 26   2007.1

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:SOC NEUROSCIENCE  

    Disrupted-In-Schizophrenia 1 (DISC1) is a candidate gene for susceptibility to schizophrenia. DISC1 is reported to interact with NudE-like (NUDEL), which forms a complex with lissencephaly-1 (LIS1) and 14-3-3 epsilon. 14-3-3 epsilon is involved in the proper localization of NUDEL and LIS1 in axons. Although the functional significance of this complex in neuronal development has been reported, the transport mechanism of the complex into axons and their functions in axon formation remain essentially unknown. Here we report that Kinesin-1, a motor protein of anterograde axonal transport, was identified as a novel DISC1-interacting molecule. DISC1 directly interacted with kinesin heavy chain of Kinesin-1. Kinesin-1 interacted with the NUDEL/LIS1/14-3-3 epsilon complex through DISC1, and these molecules localized mainly at cell bodies and partially in the distal part of the axons. DISC1 partially colocalized with Kinesin family member 5A, NUDEL, LIS1, and 14-3-3 epsilon in the growth cones. The knockdown of DISC1 by RNA interference or the dominant-negative form of DISC1 inhibited the accumulation of NUDEL, LIS1, and 14-3-3 epsilon at the axons and axon elongation. The knockdown or the dominant-negative form of Kinesin-1 inhibited the accumulation of DISC1 at the axons and axon elongation. Furthermore, the knockdown of NUDEL or LIS1 inhibited axon elongation. Together, these results indicate that DISC1 regulates the localization of NUDEL/LIS1/14-3-3 epsilon complex into the axons as a cargo receptor for axon elongation.

    DOI: 10.1523/JNEUROSCI.3826-06.2006

    Web of Science

    Scopus

    PubMed

  34. DISC1 interacts with RNA-binding proteins in messenger ribonucleoprotein complex Reviewed

    Tsuboi D, Taya S, Shinoda T, Hikita T, Kuroda S, Kaibuchi K

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 100   page: 242P - 242P   2006

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    Publishing type:Research paper (scientific journal)  

    Web of Science

  35. Plexin-A4 mediates axon-repulsive activities of both secreted and transmembrane semaphorins and plays roles in nerve fiber guidance Reviewed

    F Suto, K Ito, M Uemura, M Shimizu, Y Shinkawa, M Sanbo, T Shinoda, M Tsuboi, S Takashima, T Yagi, H Fujisawa

    JOURNAL OF NEUROSCIENCE   Vol. 25 ( 14 ) page: 3628 - 3637   2005.4

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:SOC NEUROSCIENCE  

    It has been proposed that four members of the plexin A subfamily (plexin- As; plexin- A1, -A2, -A3, and -A4) and two neuropilins (neuropilin-1 and neuropilin-2) form complexes and serve as receptors for class 3 secreted semaphorins (Semas), potent neural chemorepellents. The roles of given plexin-As in semaphorin signaling and axon guidance, however, are mostly unknown. Here, to elucidate functions of plexin-A4 in semaphorin signaling and axon guidance events in vivo, we generated plexin-A4 null mutant mice by targeted disruption of the plexin-A4 gene. Plexin-A4 mutant mice were defective in the trajectory and projection of peripheral sensory axons and sympathetic ganglion (SG) axons and the formation of the anterior commissure and the barrels. The defects in peripheral sensory and SG axons were fundamentally related to those of neuropilin-1 or Sema3A mutant embryos reported but were more moderate than the phenotype in these mutants. The growth cone collapse assay showed that dorsal root ganglion axons and SG axons of plexin-A4 mutant embryos partially lost their responsiveness to Sema3A. These results suggest that plexin-A4 plays roles in the propagation of Sema3A activities and regulation of axon guidance and that other members of the plexin-A subfamily are also involved in the propagation of Sema3A activities. Plexin-A4-deficient SG axons did not lose their responsiveness to Sema3F, suggesting that plexin-A4 serves as a Sema3A-specific receptor, at least in SG axons. In addition, the present study showed that plexin-A4 bound class 6 transmembrane semaphorins, Sema6A and Sema6B, and mediated their axon-repulsive activities, independently of neuropilin-1. Our results imply that plexin-A4 mediates multiple semaphorin signals and regulates axon guidance in vivo.

    DOI: 10.1523/JNEUROSCI.4480-04.2005

    Web of Science

    Scopus

    PubMed

  36. Roles of disrupted-in-schizophrenia-1 (DISC1) in neuronal morphologies and functions Reviewed

    Taya S, Nagai K, Shinoda T, Kaibuchi K

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 94   page: 19P - 19P   2004

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    Publishing type:Research paper (scientific journal)  

    Web of Science

  37. Inhibition of leukemia-associated RhoGEF (LARG) activity by collapsin response mediator protein-2 (CRMP-2) Reviewed

    Taya S, Shinoda T, Nagai K, Iwamatsu A, Matsuura Y, Kaibuchi K

    MOLECULAR BIOLOGY OF THE CELL   Vol. 13   page: 53A - 53A   2002.11

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    Web of Science

  38. Differential expression of plexin-A subfamily members in the mouse nervous system Reviewed

    Murakami Y, Suto F, Shimizu M, Shinoda T, Kameyama T, Fujisawa H

    DEVELOPMENTAL DYNAMICS   Vol. 220 ( 3 ) page: 246 - 258   2001.3

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    Publishing type:Research paper (scientific journal)  

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Books 6

  1. 神経幹細胞による「他力」活用: 集団的核移動の効率と細胞産生の安全

    篠田 友靖, 川上 巧, 宮田 卓樹( Role: Joint author ,  生化学 第90巻第6号、1-5.)

    2018.12 

  2. 神経前駆細胞の空間的安寧を支えるヘテロ物流

    岡本 麻友美, 篠田 友靖, 宮田 卓樹( Role: Joint author ,  細胞工学 33, 645-649.)

    2014.6 

  3. SNARE複合体形成におけるセプチンの役割

    伊藤 秀記, 篠田 友靖, 永田浩一( Role: Joint author ,  生体の科学 61, 242-246.)

    2010.6 

  4. DISC1依存的な神経軸索伸長メカニズム

    篠田 友靖( Role: Contributor ,  Medical Science Digest Vol.4, No.7, 5-6.)

    2008.6 

  5. 統合失調症脆弱性因子DISC1によるNUDEL複合体、Grb2の軸索への輸送制御

    田谷 真一郎, 篠田 友靖, 貝淵 弘三( Role: Joint author ,  細胞工学26, 410-411.)

    2007.4 

  6. DISC1 regulates neurotrophin-induced axon elongation via interaction with Grb2

    篠田 友靖( Role: Joint author)

    [s.n.]  2007 

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MISC 7

  1. Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics Reviewed

    Mingyue Jin, Oz Pomp, Tomoyasu Shinoda, Shiori Toba, Takayuki Torisawa, Ken'ya Furuta, Kazuhiro Oiwa, Takuo Yasunaga, Daiju Kitagawa, Shigeru Matsumura, Takaki Miyata, Thong Teck Tan, Bruno Reversade, Shinji Hirotsune

    SCIENTIFIC REPORTS   Vol. 7   page: 39902   2017.1

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    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    Human mutations in KATNB1 (p80) cause severe congenital cortical malformations, which encompass the clinical features of both microcephaly and lissencephaly. Although p80 plays critical roles during brain development, the underlying mechanisms remain predominately unknown. Here, we demonstrate that p80 regulates microtubule (MT) remodeling in combination with NuMA (nuclear mitotic apparatus protein) and cytoplasmic dynein. We show that p80 shuttles between the nucleus and spindle pole in synchrony with the cell cycle. Interestingly, this striking feature is shared with NuMA. Importantly, p80 is essential for aster formation and maintenance in vitro. siRNA-mediated depletion of p80 and/or NuMA induced abnormal mitotic phenotypes in cultured mouse embryonic fibroblasts and aberrant neurogenesis and neuronal migration in the mouse embryonic brain. Importantly, these results were confirmed in p80-mutant harboring patient-derived induced pluripotent stem cells and brain organoids. Taken together, our findings provide valuable insights into the pathogenesis of severe microlissencephaly, in which p80 and NuMA delineate a common pathway for neurogenesis and neuronal migration via MT organization at the centrosome/spindle pole.

    DOI: 10.1038/srep39902

    Web of Science

  2. Synergistic action of nectins and cadherins generates the mosaic cellular pattern of the olfactory epithelium Reviewed

    Sayaka Katsunuma, Hisao Honda, Tomoyasu Shinoda, Yukitaka Ishimoto, Takaki Miyata, Hiroshi Kiyonari, Takaya Abe, Ken-ichi Nibu, Yoshimi Takai, Hideru Togashi

    JOURNAL OF CELL BIOLOGY   Vol. 212 ( 5 ) page: 561 - 575   2016.2

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    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:ROCKEFELLER UNIV PRESS  

    In the olfactory epithelium (OE), olfactory cells (OCs) and supporting cells (SCs), which express different cadherins, are arranged in a characteristic mosaic pattern in which OCs are enclosed by SCs. However, the mechanism underlying this cellular patterning is unclear. Here, we show that the cellular pattern of the OE is established by cellular rearrangements during development. In the OE, OCs express nectin-2 and N-cadherin, and SCs express nectin-2, nectin-3, E-cadherin, and N-cadherin. Heterophilic trans-interaction between nectin-2 on OCs and nectin-3 on SCs preferentially recruits cadherin via a-catenin to heterotypic junctions, and the differential distributions of cadherins between junctions promote cellular intercalations, resulting in the formation of the mosaic pattern. These observations are confirmed by model cell systems, and various cellular patterns are generated by the combinatorial expression of nectins and cadherins. Collectively, the synergistic action of nectins and cadherins generates mosaic pattern, which cannot be achieved by a single mechanism.

    DOI: 10.1083/jcb.201509020

    Web of Science

  3. Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity Reviewed

    Daisuke Tsuboi, Keisuke Kuroda, Motoki Tanaka, Takashi Namba, Yukihiko Iizuka, Shinichiro Taya, Tomoyasu Shinoda, Takao Hikita, Shinsuke Muraoka, Michiro Iizuka, Ai Nimura, Akira Mizoguchi, Nobuyuki Shiina, Masahiro Sokabe, Hideyuki Okano, Katsuhiko Mikoshiba, Kozo Kaibuchi

    NATURE NEUROSCIENCE   Vol. 18 ( 5 ) page: 698 - +   2015.5

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    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    Disrupted-in-schizophrenia 1 (DISC1) is a susceptibility gene for major psychiatric disorders, including schizophrenia. DISC1 has been implicated in neurodevelopment in relation to scaffolding signal complexes. Here we used proteomic analysis to screen for DISC1 interactors and identified several RNA-binding proteins, such as hematopoietic zinc finger (HZF), that act as components of RNA-transporting granules. HZF participates in the mRNA localization of inositol-1,4,5-trisphosphate receptor type 1 (ITPR1), which plays a key role in synaptic plasticity. DISC1 colocalizes with HZF and ITPR1 mRNA in hippocampal dendrites and directly associates with neuronal mRNAs, including ITPR1 mRNA. The binding potential of DISC1 for ITPR1 mRNA is facilitated by HZF. Studies of Disc1-knockout mice have revealed that DISC1 regulates the dendritic transport of Itpr1 mRNA by directly interacting with its mRNA. The DISC1-mediated mRNA regulation is involved in synaptic plasticity. We show that DISC1 binds ITPR1 mRNA with HZF, thereby regulating its dendritic transport for synaptic plasticity.

    DOI: 10.1038/nn.3984

    Web of Science

  4. Neurogenin2-d4Venus and Gadd45g-d4Venus transgenic mice: Visualizing mitotic and migratory behaviors of cells committed to the neuronal lineage in the developing mammalian brain Reviewed

    Takumi Kawaue, Ken Sagou, Hiroshi Kiyonari, Kumiko Ota, Mayumi Okamoto, Tomoyasu Shinoda, Ayano Kawaguchi, Takaki Miyata

    DEVELOPMENT GROWTH & DIFFERENTIATION   Vol. 56 ( 4 ) page: 293 - 304   2014.5

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    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:WILEY-BLACKWELL  

    To achieve highly sensitive and comprehensive assessment of the morphology and dynamics of cells committed to the neuronal lineage in mammalian brain primordia, we generated two transgenic mouse lines expressing a destabilized (d4) Venus controlled by regulatory elements of the Neurogenin2 (Neurog2) or Gadd45g gene. In mid-embryonic neocortical walls, expression of Neurog2-d4Venus mostly overlapped with that of Neurog2 protein, with a slightly (1h) delayed onset. Although Neurog2-d4Venus and Gadd45g-d4Venus mice exhibited very similar labeling patterns in the ventricular zone (VZ), in Gadd45g-d4Venus mice cells could be visualized in more basal areas containing fully differentiated neurons, where Neurog2-d4Venus fluorescence was absent. Time-lapse monitoring revealed that most d4Venus(+) cells in the VZ had processes extending to the apical surface; many of these cells eventually retracted their apical process and migrated basally to the subventricular zone, where neurons, as well as the intermediate neurogenic progenitors that undergo terminal neuron-producing division, could be live-monitored by d4Venus fluorescence. Some d4Venus(+) VZ cells instead underwent nuclear migration to the apical surface, where they divided to generate two d4Venus(+) daughter cells, suggesting that the symmetric terminal division that gives rise to neuron pairs at the apical surface can be reliably live-monitored. Similar lineage-committed cells were observed in other developing neural regions including retina, spinal cord, and cerebellum, as well as in regions of the peripheral nervous system such as dorsal root ganglia. These mouse lines will be useful for elucidating the cellular and molecular mechanisms underlying development of the mammalian nervous system.

    DOI: 10.1111/dgd.12131

    Web of Science

  5. 神経前駆細胞の空間的安寧を支えるヘテロ物流

    岡本麻友美, 篠田友靖, 宮田卓樹

    細胞工学   ( 33 ) page: 645-649   2014

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    Language:Japanese   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)  

  6. TAG-1-assisted progenitor elongation streamlines nuclear migration to optimize subapical crowding. Reviewed

    Okamoto M, Namba T, Shinoda T, Kondo T, Watanabe T, Inoue Y, Takeuchi K, Enomoto Y, Ota K, Oda K, Wada Y, Sagou K, Saito K, Sakakibara A, Kawaguchi A, Nakajima K, Adachi T, Fujimori T, Ueda M, Hayashi S, Kaibuchi K, Miyata T

    Nat Neurosci.   ( 16 ) page: 1556-1566   2013.11

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    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)  

    DOI: 10.1038/nn.3525.

  7. 統合失調症末期海馬ニューロンにおけるDisrupted-In-Shizophrenia-1の役割(Roles of Disrupted-In-Schizophrenia-1 in the later stage of hippocampal neuron)

    坪井 大輔, 田谷 真一郎, 篠田 友靖, 匹田 貴夫, 黒田 摂子, 貝淵 弘三

    神経化学   Vol. 44 ( 2-3 ) page: 184 - 184   2005.8

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    Language:English   Publisher:日本神経化学会  

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Research Project for Joint Research, Competitive Funding, etc. 1

  1. 神経幹細胞集団の動態・形態から問う大脳皮質形成機構

    2015.12

    学内共同研究 

KAKENHI (Grants-in-Aid for Scientific Research) 9

  1. 細胞膜動態に着目した神経系前駆細胞核運動の機構解明

    Grant number:20K07223  2020.4 - 2023.3

    科学研究費助成事業  基盤研究(C)

    篠田 友靖

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    Authorship:Principal investigator 

    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    本研究「細胞膜動態に着目した神経系前駆細胞核運動の機構解明」は、脳発生に不可欠である神経系前駆細胞の核運動に焦点を当てて、核にどのような外力が加わり、その結果として核が細胞内を「動く」のかを本質的に明らかにする。これを達成するために、①核に実際に加わっている力の検出、および②核運動にともなう細胞膜の「流れ」の理解という、これまでない着眼点からこの問いに挑む。本研究により得られる成果は、細胞という閉鎖空間内をいかにして核という巨大オルガネラが動きうるのかという課題に、システム的理解・新概念をもたらすものとなる。
    大脳原基を構成する主な細胞であり、かつ将来の成熟脳の興奮性神経細胞やアストロサイトを生み出す神経系前駆細胞は、脳膜から脳室面まで達する極めて細長い構造を有し、細胞体のほとんどを核が占めている。核は細胞周期に応じて細長い細胞の中を動くことがすでに判っており、細胞骨格とそのモータータンパクが核を「運ぶ」、もしくは周囲の細胞の細胞体(核)に「押されて動く」とされている。ところが研究代表者の先行研究で核に直接外力を加えた結果、予想外に核が動きにくいことが明らかになった。この結果から、研究代表者は核周囲の細胞膜自体が核の進行方向に流動しているのではないかと考え、細胞膜・核の物性の観点、および細胞膜の「流れ」という観点で、核を動かす「力」そのものに着目し前駆細胞の核運動の本質を問うことにした。
    本年度は核を取り囲む細胞膜の流動が実際に存在するのかどうかを検証した。
    <1>改変Cortical imprint法(Shinoda et al., 2018)で神経系前駆細胞をplastic dish上に移し取り、核の進行方向に極細ガラスキャピラリーを当てがい、そのたわみ量を計測することで「核が(周囲の細胞膜を押しのけて)進もうとする力」を計測した。ガラスキャピラリーの物性測定、すなわち「どれだけの力が加わればどれだけ変形するか」は完了した。また、マイクロインジェクション用のマイクロマニピュレーターを使って、顕微鏡観察下でキャピラリー先端の「筒部分」を神経系前駆細胞に押し当てて保持する装置・手技は完成した。一方、改変Cortical imprint法下での核運動が、in vivoのそれに比較してかなり少ないという問題を見つけたので、現在培養法の改良を実施し運動量が増加するかどうかを検証している。
    改変Cortical imprint法下での核運動が、in vivoのそれに比較してかなり少ないという問題があり、現在培養法の改良を実施し対応を試みている。その他はおおむね順調に進捗している。
    現在行っている核の進行に伴う力の計測とともに、核周囲の細胞膜流動の有無と核の運動方向の関係性を検証する予定である。
    具体的には、先行研究でも使用したフェムト秒パルスレーザー照射装置を用いて、蛍光標識した細胞膜の一部をスポット状に退色させて、その領域の蛍光強度の戻りを計測する。この実験は組織培養下の脳壁内に細胞を保持したままでも実施・計測できるので、はっきりとした計測結果が得られる可能性は高いと考えている。

  2. Systems science for the ventricular zone

    Grant number:16H02457  2016.4 - 2020.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    Miyata Takaki

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    Authorship:Coinvestigator(s) 

    To elucidate how different types of cells including neural progenitors and their daughter cells collaborate dynamically to efficiently and safely construct the developing brain, live imaging, gene-manipulating experiments, and simulations were combined. This research found that tissue elasticity caused by cell densification supports passive cell-migration, that elongated fiber-like cells were bent by other cells' migration thereby contributing to tissue morphogenesis, and that external forces can also work to prevent over-migration of other cells. These results show that mechanical collaboration through cell-cell interactions facilitate efficient and safe histogenesis in 3D environment. This research also found that embryonic microglia assist neural progenitor cells and neurons in proper differentiation. Together, understanding on the mechanisms of brain development has been deepened.

  3. Analyses of pathophysiology for molecules causing mental retardation

    Grant number:23659532  2011 - 2012

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    NAGATA Koh-ichi, INAGUMA Yutaka, ITO Hidenori, SHINODA Tomoyasu, NISHIMURA Yoshiaki

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    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid) 

    A2BP1 is implicated in a variety of neurological and developmental disorders. We here prepared a specific antibody against A2BP1 and did protein expression and localization analyses in rodent brain tissues. A2BP1 was expressed in developmental stage-dependent manners in the brain. In cortical neurons, A2BP1 was accumulated mainly in the nucleus and diffusely distributed in the cell body and dendrites. In rat hippocampal neurons, while A2BP1 was found in a punctate distribution adjacent to synapses. Knockdown of A2BP1 caused abnormal neuronal migration during corticogenesis. We did similar analyses as for a polarity-related protein, Lin7, and found the importance of Lin7 in corticogenesis.

  4. Neurogenesis regulated through three-dimensional cellular movement and cell-cell interactions within the neuroepithelium

    Grant number:22111006  2010.4 - 2016.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    Miyata Takaki, KAWAGUCHI Ayano, SAKAKIBARA Akira, HASHIMOTO Mitsuhiro, SHINODA Tomoyasu, OKAMOTO Mayumi

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    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid) 

    Belonging to the "Cross-talk between moving cells and microenvironment as a basis of emerging order in multicellular system", this research project studied how movements of neural progenitor cells are coordinated to establish the safe and efficient "neurogenesis" (i.e. production of neurons to build a brain structure) without suffering from a "traffic jam" of cells in a narrow tissue-developing space. Using new techniques such as live imaging of all cells, quantitative analysis on trajectories of moving cells, and mechanical experiments, we found that cells are cleverly moving in a manner similar to "staggered commuting" (i.e. one cell goes first then the other follows). If this "crowd control" method does not work during development, brain structure cannot form normally (Nature Neuroscience, 2013). We further demonstrated brain cells' migration strategy is different between mice and ferret, suggesting that control of cellular movements may underlie brain evolution.

  5. Elasticity in neuroepithelium supports cortical development

    Grant number:17K08489  2017.4 - 2020.3

    Shinoda Tomoyasu

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    Authorship:Principal investigator 

    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

    Neural progenitor cells (NPCs), which are apicobasally elongated and densely packed in the developing brain, systematically move their nuclei/somata in a cell cycle-dependent manner, called interkinetic nuclear migration (IKNM). Our quantitative cell-biological and in silico analyses revealed that tissue elasticity mechanically assists an initial step of basalward IKNM. When the soma of an M-phase progenitor cell rounds up using actomyosin within the subapical space, a microzone within 10 μm from the surface, which is compressed and elastic because of the apical surface’s contractility, laterally pushes the densely neigh- boring processes of non-M-phase cells. The pressed processes then recoil centripetally and basally to propel the nuclei/somata of the progenitor’s daughter cells. Thus, indirect neighbor-assisted transfer of mechanical energy from mother to daughter helps efficient brain development.

  6. Mechanism for the maintenance of pseudostratified neuroepithelium

    Grant number:15K18953  2015.4 - 2017.3

    Grant-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists(B)

    Shinoda Tomoyasu

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    Neuroepithelium is widely observed in developing central nervous systems including cerebral cortex. Neural progenitor cells in neuroepithelium show cell cycle-dependent somatic motion called interkinetic nuclear migration (INM) in apico-basal direction. The purpose of this study is to elucidate how neuroepithelium keep its pseudostratified structure over time in spite of every cell shows INM. We hypothesized stresses in neuroepithelium by in toto time-lapse observation of all nuclei in developing cerebral cortex. Mathematical simulations and in vivo experiments revealed that newborn G1-phase cells in subapical area utilize the restoring force of its surrounding cells for their basal-directed nucleokinesis. These results suggest that the physical properties arised from the neuroepitelial structure assist the displacement of somata/nuclei in subapical area to sustain the pseudostratification.

  7. Mode of action of Septin-molecular complex

    Grant number:23700463  2011 - 2013

    Grant-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists(B)

    SHINODA Tomoyasu

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    Septins are a family of conserved GTP/GDP-binding proteins implicated in a variety of cellular functions such as cell cycle control and cytokinesis. We performed a screening to indentify interacting molecules for Sept4 and Sept14. By using a method combining affinity column chromatography with shotgun liquid chromatography tandem mass spectrometry, we obtained several candidates including Drebrin-1 and Cofilin-1, regulator proteins of actin cytoskeleton. As it was previously reported that Cofilin-1 is involved in cortical neuronal migration, we examined the functional involvement of Drebrin-1 for neuronal migration. Knockdown experiments by in utero electroporation showed that reduction of Drebrin-1 caused inhibition of neuronal migration. Biochemical analyses revealed the direct interaction between Sept4 and Drebrin-1, Sept14 and Cofilin-1, respectively. These results suggest that Sept4-Sept14 complex involved in neuronal migration by regulating the dynamics of actin cytoskeleton.

  8. Investigation of the molecular functions of Septin family molecules

    Grant number:20800086  2008 - 2010

    Grant-in-Aid for Young Scientists (Start-up)

    SHINODA Tomoyasu

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3302000 ( Direct Cost: \2540000 、 Indirect Cost:\762000 )

    Septin family molecules are highly conserved in eukaryotic cells. Although everal septins are specifically expressed in neuronal tissues, little is known about their physiological functions. Our research revealed that Sept14 is involved in cortical neuronal migration during corticogenesis, via interaction with Sept4.

  9. セマフォリン、プレキシン相互作用による神経回路網形成の制御

    Grant number:02J05615   2002.4 - 2005.3

    特別研究員奨励費 

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    Authorship:Principal investigator 

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Teaching Experience (On-campus) 8

  1. 発生学

    2020

  2. 肉眼解剖学

    2020

  3. 肉眼解剖学

    2019

  4. 肉眼解剖学

    2018

  5. 肉眼解剖学

    2017

  6. 肉眼解剖学

    2016

  7. 肉眼解剖学

    2015

  8. 肉眼解剖学

    2014

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Teaching Experience (Off-campus) 2

  1. 肉眼解剖学実習

    名古屋大学医学部)

  2. 生体と薬物(実習)

    名古屋大学医学部)