Updated on 2024/09/18

写真a

 
MIYATA, Takaki
 
Organization
Graduate School of Medicine Program in Integrated Medicine Anatomy and Cell Biology Professor
Institute of Liberal Arts and Sciences Headquarters Part-time faculty member
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine
Title
Professor
Contact information
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Profile
1988年3月 高知医科大学 卒業
1988年5月-1989年11月   高知医科大学・耳鼻咽喉科・研修医
1989年11月-1990年3月  高知医科大学・耳鼻咽喉科・助手
1994年4月-1995年3月 理化学研究所・ライフサイエンス筑波センター・奨励研究生
1995年4月-1996年3月 理化学研究所・ライフサイエンス筑波センター・奨励研究員
1996年4月-1997年3月 東京大学・医科学研究所・教務補佐員
1997年4月-1998年9月 日本学術振興会・海外特別研究員
(コロラド大・分子細胞発生生物学部門)
1998年10月-1999年10月  大阪大学・医学部・助手
1999年11月-2003年12月  理化学研究所・脳科学総合研究センター・研究員
2004年1月〜 名古屋大学・大学院医学系研究科・細胞生物学分野・教授(現在に至る)
2008年〜2013年 生理学研究所 多次元共同脳科学推進センター客員教授
2014年〜2016年 日本学術振興会 学術システム研究センター 専門研究員
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Degree 1

  1. 医学博士 ( 1994.9   高知医科大学 ) 

Research Interests 13

  1. brain development, neuron production, neuronal migration, layer formation, mechanical factor

  2. イメージング

  3. neuron production

  4. layer formation

  5. neuronal migration

  6. 細胞分裂

  7. 細胞極性

  8. 細胞移動

  9. 細胞間相互作用

  10. brain development

  11. brain development, neuron production, neuronal migration, layer formation, mechanical factor

  12. 運命決定

  13. 非対称分裂

Research Areas 3

  1. Others / Others  / 発生生物学

  2. Others / Others  / 神経解剖学・神経病理学

  3. Life Science / Developmental biology

Current Research Project and SDGs 1

  1. 脳細胞に学ぶ「省エネ・安全で持続可能な建築」

Research History 10

  1. 名古屋大学・大学院医学系研究科・細胞生物学分野・教授

    2004.1

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    Country:Japan

  2. 名古屋大学・大学院医学系研究科・細胞生物学分野・教授

    2004.1

  3. 理化学研究所・脳科学総合研究センター・研究員

    1999.11 - 2003.12

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    Country:Japan

  4. 大阪大学・医学部・神経機能解剖学・助手

    1998.10 - 1999.10

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    Country:Japan

  5. 日本学術振興会・海外特別研究員(コロラド大・分子細胞発生生物学部門)

    1997.4 - 1998.9

  6. 東京大学・医科学研究所・教務補佐員

    1996.4 - 1997.3

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    Country:Japan

  7. 理化学研究所・ライフサイエンス筑波センター・奨励研究員

    1995.4 - 1996.3

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    Country:Japan

  8. 理化学研究所・ライフサイエンス筑波センター・奨励研究生

    1994.4 - 1995.3

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    Country:Japan

  9. 高知医科大学・耳鼻咽喉科・助手

    1989.11 - 1990.3

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    Country:Japan

  10. 高知医科大学・耳鼻咽喉科・研修医

    1988.5 - 1989.11

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    Country:Japan

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Education 2

  1. Kochi Medical School   Graduate School, Division of Medicine

    1990.4 - 1994.3

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    Country: Japan

  2. Kochi Medical School   Faculty of Medicine

    1982.4 - 1988.3

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    Country: Japan

Professional Memberships 4

  1. 日本発生生物学会

  2. 日本神経科学会

  3. 日本解剖学会

  4. 日本機械学会

 

Papers 130

  1. CD206+ macrophages transventricularly infiltrate the early embryonic cerebral wall to differentiate into microglia Reviewed International coauthorship

    Yuki Hattori, Daisuke Kato, Futoshi Murayama, Sota Koike, Hisa Asai, Ayato Yamasaki, Yu Naito, Ayano Kawaguchi, Hiroyuki Konishi, Marco Prinz, Takahiro Masuda, Hiroaki Wake, Takaki Miyata

    Cell Reports   Vol. 42 ( 2 ) page: 112092 - 112092   2023.2

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    Authorship:Last author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.celrep.2023.112092

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  2. Transient microglial absence assists postmigratory neurons in proper differentiation. Reviewed

    Hattori Y, Naito Y, Tsugawa Y, Nonaka S, Wake H, Nagasawa T, Kawaguchi A, Miyata T.

    Nature Communications   Vol. 11   page: 1631   2020.4

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    Authorship:Last author, Corresponding author  

    DOI: 10.1038/s41467-020-15409-3

  3. Dorsal-to-Ventral Cortical Expansion Is Physically Primed by Ventral Streaming of Early Embryonic Preplate Neurons. Reviewed

    Saito K, Okamoto M, Watanabe Y, Noguchi N, Nagasaka A, Nishina Y, Shinoda T, Sakakibara A, Miyata T

    Cell Reports   Vol. 29 ( 6 ) page: 1555 - 1567.e5   2019.11

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    Authorship:Last author, Corresponding author   Language:English   Publisher:Cell Reports  

    Embryonic radial glial fibers that guide most neocortical neurons are ventrally deflected near their terminal, contributing to further expansion of the neocortical area. Saito et al. demonstrate that this fiber deflection is induced physically by a previously unrecognized ventral stream of the earliest generated preplate neurons.

    DOI: 10.1016/j.celrep.2019.09.075

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  4. Differentiating cells mechanically limit the interkinetic nuclear migration of progenitor cells to secure apical cytogenesis Reviewed

    Watanabe Yuto, Kawaue Takumi, Miyata Takaki

    DEVELOPMENT   Vol. 145 ( 14 )   2018.7

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1242/dev.162883

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

    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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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1371/journal.pbio.2004426

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  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.

    Nature Neuroscience   Vol. 16   page: 1556-1566   2013.9

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nn.3525

  7. Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum. Reviewed

    Miyata, T., Ono Y, Okamoto M, Masaoka M, Sakakibara A, Kawaguchi A, Hashimoto M, Ogawa M

    Neural Development   Vol. 5 ( 3 ) page: 1-21   2010

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  8. Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells. Reviewed

    Miyata, T., Kawaguchi, A., Saito, K., Kawano, M., Muto, T., and Ogawa, M.

    Development   Vol. 131   page: 3133-3145   2004

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  9. Asymmetric inheritance of radial glial fibers by cortical neurons. Reviewed

    Miyata, T., Kawaguchi, A., Okano, H., and Ogawa, M.

    Neuron   Vol. 31   page: 727-741   2001

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  10. NeuroD is required for differentiation of the granule cells in the cerebellum and hippocampus. Reviewed

    Miyata, T., Maeda, T., and Lee, J.E.

    Genes & Dev.   Vol. 13   page: 1647-1652   1999

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  11. Regulation of Purkinje cell alignment by Reelin as revealed with CR-50 antibody. Reviewed

    Miyata, T., Nakajima, K., Mikoshiba, K., and Ogawa, M.

    J. Neurosci.   Vol. 17   page: 3599-3609   1997

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  12. A novel preparation for histological analyses of intraventricular macrophages in the embryonic brain Reviewed

    Futoshi Murayama, Hisa Asai, Arya Kirone Patra, Hiroaki Wake, Takaki Miyata, Yuki Hattori

    Development, Growth & Differentiation     2024.6

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

    DOI: https://doi.org/10.1111/dgd.12935

  13. Endothelial cells regulate alveolar morphogenesis by constructing basement membranes acting as a scaffold for myofibroblasts Reviewed International journal

    Haruko Watanabe-Takano, Katsuhiro Kato, Eri Oguri-Nakamura, Tomohiro Ishii, Koji Kobayashi, Takahisa Murata, Koichiro Tsujikawa, Takaki Miyata, Yoshiaki Kubota, Yasuyuki Hanada, Koichi Nishiyama, Tetsuro Watabe, Reinhard Fässler, Hirotaka Ishii, Naoki Mochizuki, Shigetomo Fukuhara

    Nature Communications   Vol. 15 ( 1 ) page: 1622   2024.3

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    DOI: https://doi.org/10.1038/s41467-024-45910-y

  14. Mechanical and physical interactions involving neocortical progenitor cells Invited Reviewed

    Takaki Miyata

    Neocortical Neurogenesis in Development and Evolution     page: 119 - 136   2023.8

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    Authorship:Lead author, Last author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: https://doi.org/10.1002/9781119860914.ch7

  15. Analyzing the effect of cell rearrangement on Delta-Notch pattern formation

    Toshiki Oguma, Hisako Takigawa-Imamura, Tomoyasu Shinoda, Shuntaro Ogura, Akiyoshi Uemura, Takaki Miyata, Philip K. Maini, Takashi Miura

    Physical Review E   Vol. 107 ( 6 ) page: 064404   2023.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Physical Society (APS)  

    DOI: 10.1103/PhysRevE.107.064404

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    Other Link: http://harvest.aps.org/v2/journals/articles/10.1103/PhysRevE.107.064404/fulltext

  16. Actin crosslinking by α-actinin averts viscous dissipation of myosin force transmission in stress fibers. Reviewed

    Katsuta H, Okuda S, Nagayama K, Machiyama H, Kidoaki S, Kato M, Sokabe M, Miyata T, Hirata H

    iScience   Vol. 26 ( 3 ) page: 106090   2023.3

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

    Contractile force generated in actomyosin stress fibers (SFs) is transmitted along SFs to the extracellular matrix (ECM), which contributes to cell migration and sensing of ECM rigidity. In this study, we show that efficient force transmission along SFs relies on actin crosslinking by α-actinin. Upon reduction of α-actinin-mediated crosslinks, the myosin II activity induced flows of actin filaments and myosin II along SFs, leading to a decrease in traction force exertion to ECM. The fluidized SFs maintained their cable integrity probably through enhanced actin polymerization throughout SFs. A computational modeling analysis suggested that lowering the density of actin crosslinks caused viscous slippage of actin filaments in SFs and, thereby, dissipated myosin-generated force transmitting along SFs. As a cellular scale outcome, α-actinin depletion attenuated the ECM-rigidity-dependent difference in cell migration speed, which suggested that α-actinin-modulated SF mechanics is involved in the cellular response to ECM rigidity.

    DOI: 10.1016/j.isci.2023.106090

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  17. Functional Cooperation of α-Synuclein and Tau Is Essential for Proper Corticogenesis. Reviewed

    Wang S, Fu Y, Miyata T, Matsumoto S, Shinoda T, Itoh K, Harada A, Hirotsune S, Jin M

    The Journal of neuroscience : the official journal of the Society for Neuroscience   Vol. 42 ( 37 ) page: 7031 - 7046   2022.9

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    Language:English   Publisher:Journal of Neuroscience  

    Alpha-synuclein (aSyn) and tau are abundant multifunctional neuronal proteins, and their intracellular deposits have been linked to many neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Despite the disease relevance, their physiological roles remain elusive, as mice with knock-out of either of these genes do not exhibit overt phenotypes. To reveal functional cooperation, we generated aSyn2/2tau2/2 double-knock-out mice and characterized the functional cross talk between these proteins during brain development. Intriguingly, deletion of aSyn and tau reduced Notch signaling and accelerated interkinetic nuclear migration of G2 phase at early embryonic stage. This significantly altered the balance between the proliferative and neurogenic divisions of progenitor cells, resulting in an overproduction of early born neurons and enhanced neurogenesis, by which the brain size was enlarged during the embryonic stage in both sexes. On the other hand, a reduction in the number of neural progenitor cells in the middle stage of corticogenesis diminished subsequent gliogenesis in the aSyn2/2tau2/2 cortex. Additionally, the expansion and maturation of macroglial cells (astrocytes and oligodendrocytes) were suppressed in the aSyn2/2tau2/2 postnatal brain, which in turn reduced the male aSyn2/2tau2/2 brain size and cortical thickness to less than the control values. Our study identifies important functional cooperation of aSyn and tau during corticogenesis.

    DOI: 10.1523/JNEUROSCI.0396-22.2022

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  18. Border-associated macrophages transventricularly infiltrate the early embryonic cerebral wall to differentiate into microglia

    Yuki Hattori, Daisuke Kato, Futoshi Murayama, Sota Koike, Yu Naito, Ayano Kawaguchi, Hiroaki Wake, Takaki Miyata

        2022.7

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    Publisher:Cold Spring Harbor Laboratory  

    Summary

    The relationships between microglia and macrophages, especially their lineage segregation outside the yolk sac, have been recently explored, providing a model in which a conversion from macrophages seeds microglia during brain development. However, spatiotemporal evidence to support such microglial seeding and to explain how it occurs has not been obtained. By cell tracking via slice culture, intravital imaging, and Flash tag-mediated labeling, we found that a group of intraventricular macrophages belonging to border-associated macrophages (BAMs), which were abundantly observed along the inner surface of the mouse cerebral wall at embryonic day 12, frequently entered the brain wall. Immunohistochemistry of the tracked cells showed that postinfiltrative BAMs acquired microglial properties while losing a macrophage phenotype. We also found that the intraventricular BAMs were supplied transepithelially from the roof plate. Thus, this study demonstrates that the “roof plate→ventricle→cerebral wall” route is an essential path for microglial colonization into the embryonic mouse brain.

    DOI: 10.1101/2022.07.27.501563

  19. Mid1 is associated with androgen-dependent axonal vulnerability of motor neurons in spinal and bulbar muscular atrophy. Reviewed

    Ogura Y, Sahashi K, Hirunagi T, Iida M, Miyata T, Katsuno M

    Cell death & disease   Vol. 13 ( 7 ) page: 601   2022.7

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    Spinal and bulbar muscular atrophy (SBMA) is an adult-onset hereditary neurodegenerative disease caused by the expansions of CAG repeats in the androgen receptor (AR) gene. Androgen-dependent nuclear accumulation of pathogenic AR protein causes degeneration of lower motor neurons, leading to progressive muscle weakness and atrophy. While the successful induction of SBMA-like pathology has been achieved in mouse models, mechanisms underlying motor neuron vulnerability remain unclear. In the present study, we performed a transcriptome-based screening for genes expressed exclusively in motor neurons and dysregulated in the spinal cord of SBMA mice. We found upregulation of Mid1 encoding a microtubule-associated RNA binding protein which facilitates the translation of CAG-expanded mRNAs. Based on the finding that lower motor neurons begin expressing Mid1 during embryonic stages, we developed an organotypic slice culture system of the spinal cord obtained from SBMA mouse fetuses to study the pathogenic role of Mid1 in SBMA motor neurons. Impairment of axonal regeneration arose in the spinal cord culture in SBMA mice in an androgen-dependent manner, but not in mice with non-CAG-expanded AR, and was either exacerbated or ameliorated by Mid1 overexpression or knockdown, respectively. Hence, an early Mid1 expression confers vulnerability to motor neurons, at least by inducing axonogenesis defects, in SBMA.

    DOI: 10.1038/s41419-022-05001-6

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  20. Actin-binding protein filamin-A drives tau aggregation and contributes to progressive supranuclear palsy pathology. Reviewed

    Tsujikawa K, Hamanaka K, Riku Y, Hattori Y, Hara N, Iguchi Y, Ishigaki S, Hashizume A, Miyatake S, Mitsuhashi S, Miyazaki Y, Kataoka M, Jiayi L, Yasui K, Kuru S, Koike H, Kobayashi K, Sahara N, Ozaki N, Yoshida M, Kakita A, Saito Y, Iwasaki Y, Miyashita A, Iwatsubo T, Japanese Alzheimer’s Disease Neuroimaging Initiative (J-ADNI), Ikeuchi T, Japanese Longitudinal Biomarker Study in PSP and CBD (JALPAC) Consortium, Miyata T, Sobue G, Matsumoto N, Sahashi K, Katsuno M

    Science advances   Vol. 8 ( 21 ) page: eabm5029   2022.5

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    While amyloid-β lies upstream of tau pathology in Alzheimer’s disease, key drivers for other tauopathies, including progressive supranuclear palsy (PSP), are largely unknown. Various tau mutations are known to facilitate tau aggregation, but how the nonmutated tau, which most cases with PSP share, increases its propensity to aggregate in neurons and glial cells has remained elusive. Here, we identified genetic variations and protein abundance of filamin-A in the PSP brains without tau mutations. We provided in vivo biochemical evidence that increased filamin-A levels enhance the phosphorylation and insolubility of tau through interacting actin filaments. In addition, reduction of filamin-A corrected aberrant tau levels in the culture cells from PSP cases. Moreover, transgenic mice carrying human filamin-A recapitulated tau pathology in the neurons. Our data highlight that filamin-A promotes tau aggregation, providing a potential mechanism by which filamin-A contributes to PSP pathology.

    DOI: 10.1126/sciadv.abm5029

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  21. Embryonic Pericytes Promote Microglial Homeostasis and Their Effects on Neural Progenitors in the Developing Cerebral Cortex. Reviewed

    Hattori Y, Itoh H, Tsugawa Y, Nishida Y, Kurata K, Uemura A, Miyata T

    Journal of Neuroscience   Vol. 42 ( 3 ) page: 362 - 376   2022.1

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    Authorship:Last author   Language:English   Publisher:The Journal of neuroscience : the official journal of the Society for Neuroscience  

    Multifaceted microglial functions in the developing brain, such as promoting the differentiation of neural progenitors and contributing to the positioning and survival of neurons, have been progressively revealed. Although previous studies have noted the relationship between vascular endothelial cells and microglia in the developing brain, little attention has been given to the importance of pericytes, the mural cells surrounding endothelial cells. In this study, we attempted to dissect the role of pericytes in microglial distribution and function in developing mouse brains. Our immunohistochemical analysis showed that approximately half of the microglia attached to capillaries in the cerebral walls. Notably, a magnified observation of the position of microglia, vascular endothelial cells and pericytes demonstrated that microglia were preferentially associated with pericytes that covered 79.8% of the total capillary surface area. Through in vivo pericyte depletion induced by the intraventricular administration of a neutralizing antibody against platelet-derived growth factor receptor (PDGFR)β (clone APB5), we found that microglial density was markedly decreased compared with that in control antibody-treated brains because of their low proliferative capacity. Moreover, in vitro coculture of isolated CD11b+ microglia and NG2+PDGFRα- cells, which are mostly composed of pericytes, from parenchymal cells indicated that pericytes promote microglial proliferation via the production of soluble factors. Furthermore, pericyte depletion by APB5 treatment resulted in a failure of microglia to promote the differentiation of neural stem cells into intermediate progenitors. Taken together, our findings suggest that pericytes facilitate microglial homeostasis in the developing brains, thereby indirectly supporting microglial effects on neural progenitors.SIGNIFICANCE STATEMENT This study highlights the novel effect of pericytes on microglia in the developing mouse brain. Through multiple analyses using an in vivo pericyte depletion mouse model and an in vitro coculture study of isolated pericytes and microglia from parenchymal cells, we demonstrated that pericytes contribute to microglial proliferation and support microglia in efficiently promoting the differentiation of neural stem cells into intermediate progenitors. Our present data provide evidence that pericytes function not only in the maintenance of cerebral microcirculation and blood brain barrier (BBB) integrity but also in microglial homeostasis in the developing cerebral walls. These findings will expand our knowledge and help elucidate the mechanism of brain development both in healthy and disease conditions.

    DOI: 10.1523/JNEUROSCI.1201-21.2021

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  22. Developmentally interdependent stretcher-compressor relationship between the embryonic brain and the surrounding scalp in the preosteogenic head. Reviewed

    Tsujikawa K, Saito K, Nagasaka A, Miyata T

    Developmental Dynamics     2022.1

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    Background: How developing brains mechanically interact with the surrounding embryonic scalp layers (ie, epidermal and mesenchymal) in the preosteogenic head remains unknown. Between embryonic day (E) 11 and E13 in mice, before ossification starts in the skull vault, the angle between the pons and the medulla decreases, raising the possibility that when the elastic scalp is directly pushed outward by the growing brain and thus stretched, it recoils inward in response, thereby confining and folding the brain. Results: Stress-release tests showed that the E11-13 scalp recoiled and that the in vivo prestretch prerequisite for this recoil was physically dependent on the brain (pressurization at 77-93 Pa) and on actomyosin and elastin within the scalp. In scalp-removed heads, brainstem folding was reduced, and the spreading of ink from the lateral ventricle to the spinal cord that occurred in scalp-intact embryos (with >5 μL injection) was lost, suggesting roles of the embryonic scalp in brain morphogenesis and cerebrospinal fluid homeostasis. Under nonstretched conditions, scalp cell proliferation declined, while the restretching of the shrunken scalp rescued scalp cell proliferation. Conclusions: In the embryonic mouse head before ossification, a stretcher-compressor relationship elastically develops between the brain and the scalp, underlying their mechanically interdependent development.

    DOI: 10.1002/dvdy.451

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  23. Comparison of the Mechanical Properties Between the Convex and Concave Inner/Apical Surfaces of the Developing Cerebrum Reviewed

    Frontiers in Cell and Developmental Biology   Vol. 9   2021.7

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    DOI: 10.3389/fcell.2021.702068.

  24. A mouse model of microglia-specific ablation in the embryonic central nervous system. Reviewed

    Li C, Konishi H, Nishiwaki K, Sato K, Miyata T, Kiyama H

    Neuroscience Research     2021.6

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    Language:English   Publisher:Neuroscience Research  

    Microglia, which migrate into the central nervous system (CNS) during the early embryonic stages, are considered to play various roles in CNS development. However, their embryonic roles are largely unknown, partly due to the lack of an effective microglial ablation system in the embryo. Here, we show a microglial ablation model by injecting diphtheria toxin (DT) into the amniotic fluid of Siglechdtr mice, in which the gene encoding DT receptor is knocked into the microglia-specific gene locus Siglech. We revealed that embryonic microglia were depleted for several days throughout the CNS, including some regions where microglia transiently accumulated, at any embryonic time point from embryonic day 10.5, when microglia colonize the CNS. This ablation system was specific for microglia because CNS-associated macrophages, which are a distinct population from microglia that reside in the CNS interfaces such as meninges, were unaffected. Therefore, this microglial ablation system is highly effective for studying the embryonic functions of microglia.

    DOI: 10.1016/j.neures.2021.06.002

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  25. 大脳皮質の発生における力学 Invited

    宮田卓樹

      Vol. 38   page: 1510 - 1512   2020.12

  26. Two-photon microscopic observation of cell-production dynamics in the developing mammalian neocortex in utero. Invited 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 & Differentiation   Vol. 62   page: 118 - 128   2020.1

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    DOI: 10.1111/dgd.12648.

  27. Meflin-positive cancer-associated fibroblasts inhibit pancreatic carcinogenesis Invited Reviewed International coauthorship

    Mizutani Y, Kobayashi H, Iida T, Asai N, Masamune A, Hara A, Esaki N, Ushida K, Mii S, Shiraki Y, Ando K, Weng L, Ishihara S, Ponik SM, Conklin MH, Haga H, Nagasaka A, Miyata T, Matsuyama M, Kobayashi T, Fujii T, Yamada S, Yamaguchi J, Wang T, Woods SL, Worthley D, Shimamura T, Fujishiro M, Hirooka Y, Takahashi M, and Enomoto A

    Cancer Research   Vol. 79   page: 5367 - 5381   2019.10

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1158/0008-5472

  28. Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin in Cardiac Tissue Repair and the Development of Diastolic Dysfunction

    Hara Akitoshi, Kobayashi Hiroki, Asai Naoya, Saito Shigeyoshi, Higuchi Takahiro, Kato Katsuhiro, Okumura Takahiro, Bando Yasuko K., Takefuji Mikito, Mizutani Yasuyuki, Miyai Yuki, Saito Shoji, Maruyama Shoichi, Maeda Keiko, Ouchi Noriyuki, Nagasaka Arata, Miyata Takaki, Mii Shinji, Kioka Noriyuki, Worthley Daniel L., Murohara Toyoaki, Takahashi Masahide, Enomoto Atsushi

    CIRCULATION RESEARCH   Vol. 125 ( 4 ) page: 414-430   2019.8

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

    DOI: 10.1161/CIRCRESAHA.119.314806

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

    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   2019.6

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

    DOI: 10.1038/s41467-019-10730-y

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  30. [Production Logistics and Crowd Dynamics in the Developing Cerebral Cortex].

    Miyata T

    Brain and nerve = Shinkei kenkyu no shinpo   Vol. 71 ( 4 ) page: 415-421   2019.4

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    DOI: 10.11477/mf.1416201287

    PubMed

  31. 大脳皮質形成の生産物流とクラウドダイナミクス Invited Reviewed

    宮田 卓樹

      Vol. 71   page: 415 - 421   2019.4

  32. Novel Development of Diabetic Retinopathy Research by Integrated Approach Reviewed

    植村明嘉, 小椋俊太郎, 小椋俊太郎, 倉田薫里, 小峯祐美, 大矢恵, 井上奈緒美, 井上奈緒美, 小椋祐一郎, 高瀬弘嗣, 宮田卓樹, 福嶋葉子, 楠原仙太郎, 平島正則, 池田わたる, 南敬, 渋谷正史, 吉田富, MANN Fanny, 酒井秀人, 奈良裕美, YANCOPOULOS George D, WIEGAND Stanley J, KIM Pilhan, KOH Gou Young, 西川伸一

    日本眼科学会雑誌   Vol. 123 ( 3 ) page: 312 - 336   2019

  33. 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 Invited Reviewed

    篠田 友靖,川上 巧,宮田 卓樹

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

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  34. Embryonic Neocortical Microglia Express Toll-Like Receptor 9 and Respond to Plasmid DNA Injected into the Ventricle: Technical Considerations Regarding Microglial Distribution in Electroporated Brain Walls.

    Hattori Y, Miyata T

    eNeuro   Vol. 5 ( 6 )   2018.11

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    DOI: 10.1523/ENEURO.0312-18.2018

    PubMed

  35. Microglia extensively survey the developing cortex via the CXCL12/CXCR4 system to help neural progenitors to acquire differentiated properties.

    Hattori Y, Miyata T

    Genes to cells : devoted to molecular & cellular mechanisms     2018.8

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    DOI: 10.1111/gtc.12632

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  36. Role of extrinsic mechanical force in the development of the RA-I tactile mechanoreceptor

    Trung Quang Pham, Kawaue Takumi, Hoshi Takayuki, Tanaka Yoshihiro, Miyata Tataki, Sano Akihito

    SCIENTIFIC REPORTS   Vol. 8   2018.7

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    DOI: 10.1038/s41598-018-29390-x

    Web of Science

  37. Synaptic transmission from subplate neurons controls radial migration of neocortical neurons

    Ohtaka-Maruyama Chiaki, Okamoto Mayumi, Endo Kentaro, Oshima Minori, Kaneko Noe, Yura Kei, Okado Haruo, Miyata Takaki, Maeda Nobuaki

    SCIENCE   Vol. 360 ( 6386 ) page: 313-316   2018.4

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    DOI: 10.1126/science.aar2866

    Web of Science

    PubMed

  38. Radial Glial Fibers Promote Neuronal Migration and Functional Recovery after Neonatal Brain Injury Reviewed

    Jinnou H, Sawada M, Kawase K, Kaneko N, Herranz-Pérez V, Miyamoto T, Kawaue T, Miyata T, Tabata Y, Akaike T, García-Verdugo JM, Ajioka I, Saitoh S, Sawamoto K.

    Cell Stem Cell.   Vol. 22 ( 1 ) page: 128–137.e9   2018.1

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    DOI: http://dx.doi.org/10.1016/j.stem.2017.11.005

  39. Neural Progenitor Cells Undergoing Yap/Tead-Mediated Enhanced Self-Renewal Form Heterotopias More Easily in the Diencephalon than in the Telencephalon. Reviewed

    Saito K, Kawasoe R, Sasaki H, Kawaguchi A, Miyata T.

    Neurochemical Research   Vol. 43 ( 1 ) page: 171–180   2018.1

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    DOI: 10.1007/s11064-017-2390-x

  40. 神経上皮 – 大脳皮質の原構造におけるクラウドダイナミクスと組織力学 Reviewed

    宮田卓樹

    生体の科学   Vol. 68 ( 1 ) page: 4-8   2017.2

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  41. Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown. Reviewed

    Ogura S, Kurata K, Hattori Y, Takase H, Ishiguro-Oonuma T, Hwang Y, Ahn S, Park I, Ikeda W, Kusuhara S, Fukushima Y, Nara H, Sakai H, Fujiwara T, Matsushita J, Ema M, Hirashima M, Minami T, Shibuya M, Takakura N, Kim P, Miyata T, Ogura Y, Uemura A.

    JCI Insight.   Vol. 2   page: e90905   2017.2

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    DOI: 10.1172/jci.insight.90905.

  42. Reelin transiently promotes N-cadherin-dependent neuronal adhesion during mouse cortical development. Reviewed

    Matsunaga Y, Noda M, Murakawa H, Hayashi K, Nagasaka A, Inoue S, Miyata T, Miura T, Kubo K, and Nakajima K.

    . Proc. Natl. Acad. Sci. U.S.A.     2017.2

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    DOI: 10.1073/pnas.1615215114

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

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

    Sci Rep.   Vol. 7   page: 39902   2017.1

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    DOI: 10.1038/srep39902.

  44. 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 T, Nagayama K, Matsumoto T, Ueno N, Kawaguchi A and Miyata T.

    Front. Cell Dev. Biol.   Vol. 4   page: 139   2016.11

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    DOI: 10.3389/fcell.2016.00139

  45. Two-Photon imaging of DiO-labelled Meissner corpuscle in living mouse's fingertip. Reviewed

    Pham TQ, Hoshi T, Tanaka Y, Sano A, Kawaue T, Miyata T.

    IEEE Trans Haptics.   Vol. 9 ( 4 ) page: 483-491   2016.6

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    DOI: 10.1109/TOH.2016.2574718

  46. PDK1-Akt pathway regulates radial neuronal migration and microtubules in the developing mouse neocortex. Reviewed

    Itoh, Y., Higuchi, M., Oishi, K., Kishi, Y., Okazaki, T., Sakai, H., Miyata, T., Nakajima, K. and Gotoh, Y.

    PNAS   Vol. 113   page: E2955-64   2016.5

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    DOI: 10.1073/pnas.1516321113

  47. Cell-cycle-independent transitions in temporal identity of mammalian neural progenitor cells. Reviewed

    Okamoto, M., Miyata, T., Konno, D., Ueda, H. R., Kasukawa, T., Hashimoto, M., Matsuzaki, F., Kawaguchi, A.

    Nat Commun.   Vol. 7   page: 11349   2016.4

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    DOI: 10.1038/ncomms11349.

  48. 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: 10.1083/jcb.201509020.

  49. Consensus paper: Cerebellar development. Reviewed

    Leto, K., Arancillo, M., Becker, E. B. E., Buffo, A., Chiang, C., Ding, B., Dobyns, W. B., Dusart, I., Haldipur, P., Hatten, M. E., Hoshino, M., Joyner, A. L., Kano, M., Kilpatrick, D. L., Koibuchi, N., Marion, S., Martinez, S., Millen, K. J., Millner, T. O., Miyata, T., Parmigiani, E., Schilling, K., Sekerkova, G., Sillitoe, R. V., Sotelo, C., Uesaka, N., Wefers, A., Wingate, R. J. T., Hawkes, R.

    The Cerebellum     2015.10

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    he development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes of cerebellar ontogenesis, highlighting the neurogenic strategies used by developing progenitors, the genetic programs involved in cell fate specification, the progressive changes of structural organization, and some of the better-known abnormalities associated with developmental disorders of the cerebellum.

    DOI: 10.1007/s12311-015-0724-2

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

    Miyata, T., Okamoto, M., Shinoda, T., Kawaguchi, A

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

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    DOI: 10.3389/fncel.2014.00473

  51. 神経幹細胞の集団的な核移動

    宮田卓樹

    脳神経系の再生医学ー発生と再生の融合的新展開ー(診断と治療社 再生医療シリーズ)     page: 50-54   2015.1

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  52. Programmable wireless light-emitting diode stimulator for chronic stimulation of optogenetic molecules in freely moving mice. Reviewed

    Hashimoto, M., Hata, A., Miyata, T., Hirase, H.

    Programmable wireless light-emitting diode stimulator for chronic stimulation of optogenetic molecules in freely moving mice.   Vol. 1   page: 011002   2014.5

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    DOI: 10.1117/1.NPh.1.1.011002

  53. Dynamics of centrosome translocation and microtubule organization in neocortical neurons during distinct modes of polarization. Reviewed

    Sakakibara, A., Sato, T., Ando, R., Noguchi, N., Masaoka, M., Miyata, T.

    Cereb. Cortexdoi:10.1093/cercor/bhs411     2014

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    DOI: doi:10.1093/cercor/bhs411

  54. 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.   Vol. 83   page: 25-32   2014

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  55. 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   Vol. 56   page: 293-304   2014

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  56. Pioneering axons regulate neuronal polarization in the devveloping cerebral cortex. Reviewed

    Namba, T., Kibe, Y., Funahashi, Y., Nakamuta, S., Takano, T., Ueno, T., Shimada, A., Kozawa, S., Okamoto, M., Shimoda, Y., Oda, K., Wada, Y., Masuda, T., Sakakibara, A., Igarashi, M., Miyata, T., Faivre-Sarrailh, C., Takeuchi, K., Kaibuchi, K.

    Neuron   Vol. 81   page: 814-829   2014

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  57. 脳形成を下支えする神経前駆細胞の核移動

    宮田卓樹,岡本麻友美

    生体の科学 (特集「器官の発生と再生の基礎」)   Vol. 65   page: 203-207   2014

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  58. Overview (特集「動く細胞・群れる細胞」)

    宮田卓樹

    細胞工学   ( 33 ) page: 590-592   2014

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  59. 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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  60. 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.     page: 293-304   2014

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    DOI: 10.1111/dgd.12131

  61. Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation. Reviewed

    Ageta-Ishihara, N., Miyata, T., Ohshima, C., Watanabe, M., Sato, Y., Hamamura, Y., Higashijima, T., Mazitschek, R., Bito, H., Kinoshita, M.

    Nature Communications   Vol. 4   page: 2532   2013.10

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    DOI: 10.1038/ncomms3532

  62. Improved orange and red Ca2+ indicators and photophysical considerations for optogenetic applications. Reviewed

    Wu, J , Liu, L , Matsuda, T , Zao, Y, Rebane, A , Drobizhev, M , Chang, Y-F , Araki, S , Arai, Y , March, K , Thomas, HE, Sagou, K , Miyata, T, Nagai, T , Li, W-H , and Campbell, RE

    ACS Chem. Neurosci.     2013.3

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    DOI: 10.1021/cn400012b

  63. Shootin1 acts in concert with KIF20B to promote polarization of migrating neurons. Reviewed

    Sapir, T., Levy, T., Sakakibara, A., Rabinkov, A., Miyata, T., Reiner, O.

    J. Neurosci.   Vol. 33   page: 11932-11948   2013

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    DOI: 10.1523/JNEUROSCI.5425-12.2013

  64. Reelin-dependent ApoER2 downregulation uncouples newborn neurons from progenitor cells. Reviewed

    Pérez-Martínez, F.J., Luque-Río, A., Sakakibara, A., Hattori, M., Miyata, T., Luque, J. M.

    Biology Open     2012.10

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    DOI: 10.1242

  65. WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration. Reviewed

    Xie, M.-J., Yagi, H., Kuroda, K., Wang, C.-C., Komada, M., Zhao, H., Sakakibara, A., Miyata, T. Nagata, K., Iguchi, T., Sato, M.

    Cereb. Cortex     page: doi:10.1093   2012

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    DOI: 10.1093

  66. Local Application of Neurotrophins Specifies Axons Through Inositol 1,4,5-Trisphosphate, Calcium, and Ca2+/Calmodulin-Dependent Protein kinases. Reviewed

    Nakamuta S, Funahashi Y, Namba T, Arimura N, Picciotto M R, Tokumitsu H, Soderling T R, Sakakibara A, Miyata T, Kamiguchi H, and Kaibuchi K.

    Science Signaling   Vol. 4   2011.11

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    DOI: 10.1126/scisignal.2002011

  67. 小脳皮質形成メカニズムの解明をめざして:プルキンエ細胞の移動と配置の過程に関する新知見 Invited

    宮田卓樹

    ブレインサイエンスレビュー   Vol. 2011   page: 91-110   2011

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  68. T. Girdin maintains the stemness of glioblastoma stem cells. Reviewed

    Natsume, S., Kato, T., Kinjo, S., Enomoto, A., Toda, H., Shimato, S., Ohka F, Motomura K, Kondo Y, Miyata T, Takahashi M, Wakabayashi T.

    Oncogene   ( 31 ) page: 2715-2724   2011

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    DOI: 10.1038/onc.2011

  69. Mechanisms that regulates the number of neurons during mouse neocortical development Reviewed

    Takaki Miyata, Daichi Kawaguchi, Ayano Kawaguchi, Yukiko Gotoh

    Current Opinion in Neurobiology   Vol. 20   page: 1-7   2010

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  70. Periventricular Notch activation and asymmetric Ngn2 and Tbr2 expression in pair-generated neocortical daughter cells Reviewed

    Ochiai, W., Nakatani, S., Takahara, T., Kainuma, M., Masaoka, M., Minobe, S., Namihira, M., Nakashima, K., Sakakibara, A., Ogawa, M., Miyata, T

    Mol. Cell. Neurosci.   Vol. 40   page: 225-233   2009

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  71. Downregulation of functional Reelin receptors in projection neurons implies that primary Reelin action occurs at early/premigratory stages. Reviewed

    Uchida T, Baba A, Pérez-Martínez FJ, Hibi T, Miyata T, Luque JM, Nakajima K, Hattori M.

    J Neurosci.   Vol. 29   page: 10653-10662   2009

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  72. Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis. Reviewed

    Saito K, Dubreuil V, Arai Y, Wilsch-Bräuninger M, Schwudke D, Saher G, Miyata T, Breier G, Thiele C, Shevchenko A, Nave KA, Huttner WB.

    Proc Natl Acad Sci U S A.   Vol. 106   page: 8350-8355   2009

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  73. Rac is involved in the interkinetic nuclear migration of cortical progenitor cells. Reviewed

    Minobe, S., Sakakibara, A., Ohdachi, T., Kanda, R., Kimura, M., Nakatani, S., Tadokoro, R., Ochiai, W., Nishizawa, Y., Mizoguchi, A., Kawauchi, T., Miyata, T.

    Neurosci. Res.   Vol. 63   page: 294-301   2009

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  74. Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Reviewed

    Konno, D., Shioi, G., Shitamukai, A., Mori, A., Kiyonari, H., Miyata, T. and Matsuzaki, F

    Nat. Cell Biol.   Vol. 10   page: 93-101   2008

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  75. Mind bomb 1-experssing intermediate progenitors generate Notch signaling to maintain radial glial cells. Reviewed

    Yoon, K.-J., Koo, B.-K., Jeong, H.-W., Ghim, J., Kwon, M.-C., Moon, J.-S., Miyata, T., Kong, Y.-Y.

    Neuron   Vol. 58   page: 519-531   2008

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  76. 大脳皮質における層形成 Invited

    宮田卓樹

    実験医学   Vol. 26   page: 1875-1879   2008

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  77. Cell-cycle-specific nestin expression coordinates with morphological changes in embryonic cortical neural progenitors Reviewed

    Sunabori, T., Tokunaga, A., Nagai, T., Sawamoto, K., Okabe, M., Miyawaki, A., Matsuzaki, Y., Miyata, T., Okano, H.

    J. Cell Sci.   Vol. 121   page: 1204-1212   2008

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  78. Development of three-dimensional srchitecture of the neuroepithelium: Role of pseudostratification and cellular 'community' Reviewed

    Takaki Miyata

    Dev. Growth Differ.   Vol. 50   page: S105-S112   2008

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  79. Visualizing spatiotemporal dynamics of multicellular cell-cycle progression Reviewed

    Sakaue-Sawano, A., Kurokawa, H., Morimura, T., Hanyu, A., Hama, H., Osawa, H., Kashiwagi, S., Fukami, K., Miyata, T., Miyoshi, H., Imamura, T., Ogawa, M., Masai, H. and Miyawaki, A.

    Cell   Vol. 132   page: 487-498   2008

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  80. Photopic electroretinograms of mGluR6-deficient mice.

    Koyasu T, Kondo M, Miyata K, Ueno S, Miyata T, Nishizawa Y, Terasaki H

    Curr Eye Res.   Vol. 33   page: 91-99   2008

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    DOI: 10.1080/027136807018

  81. Pax6 transcription factor regulates interkinetic nuclear movement in cortical progenitor cells via centrosomal stabilization Reviewed

    Tamai, H., Shinohara, H., Miyata, T., Saito, K., Nishizawa, Y., Nomura, T. and Osumi, N

    Genes to Cells   Vol. 12   page: 983-996   2007.9

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  82. Morphology and mechanics of daughter cells "delaminating" from the ventricular zone of the developing neocortex Reviewed

    Takaki Miyata

    Cell Adhesion & Migration   Vol. 1 ( 2 ) page: 99-101   2007.4

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  83. 大脳皮質原基におけるニューロンの誕生と旅立ち Invited

    宮田卓樹

    実験医学   Vol. 25 ( 3 ) page: 333-337   2007.2

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  84. Transformation of pin-like ventricular zone cells into cortical neurons. Reviewed

    Ochiai, W., Minobe, S., Ogawa, M., Miyata, T.

    Neurosci. Res.   Vol. 57   page: 326-329   2007

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  85. Survey of the morphogenetic dynamics of the ventricular surface of the developing mouse cortex Reviewed

    Nishizawa, Y., Imafuku, H., Saito, K., Kanda, R., Kimura, M., Minobe, S., Miyazaki, F., Kawakatsu, S., Masaoka, M., Ogawa, M. and Miyata, T

    Dev. Dyn.   Vol. 236   page: 3061-3070   2007

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  86. 大脳皮質形成過程における細胞動態の3次元ライブ観察 Invited Reviewed

    宮田卓樹

    顕微鏡   Vol. 42   page: 174-179   2007

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  87. Twisting of neocortical progenitor cells underlies a spring-like mechanism for daughter cell migration. Reviewed

    Miyata, T., Ogawa, M.

    Curr. Biol.   Vol. 17   page: 146-151   2007

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  88. The c-Jun N-terminal kinase activator dual leucine zipper kinase regulates axon growth and neuronal migration in the developing cerebral cortex. Reviewed

    Hirai, S., Cui, DF., Miyata, T., Ogawa, M., Kiyonari, H., Suda, Y., Aizawa, S., Banda, Y. and Ohno, S

    J Neurosci   Vol. 26   page: 11992-12002   2006

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  89. 移動ニューロンの骨格と接着:神経上皮長屋の屋根裏部屋にて Invited

    宮田卓樹

    蛋白質核酸酵素   Vol. 51   page: 721-726   2006

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  90. Inactivation of aPKCλ results in the loss of adherens junctions in neuroepithelial cells without affecting neurogenesis in mouse neocortex. Reviewed

    Imai, F., Hirai, S., Akimoto, K., Koyama, H., Miyata, T., Ogawa, M., Noguchi, S., Sasaoka, T., Noda, T, and Ohno, S.

    Development   Vol. 133   page: 1735-1744,   2006

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  91. Dynamic behavior of individual cells in developing organotypic brain slices revealed by the photoconvertable protein Kaede. Reviewed

    Muto, T.,, Miyata, T., Kashiwagi, S., Miyawaki, A., and Ogawa, M.

    Exp. Neurol   Vol. 200   page: 430-437   2006

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  92. Induction of oligodendrocyte progenitors in dorsal forebrain by intraventricular microinjection of FGF-2. Reviewed

    Naruse, M., Nakahira, E., Miyata, T., Hitoshi, S., Ikenaka, K., and Bansai, R

    Dev. Biol   Vol. 297   page: 262-273   2006

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  93. Midkine, a heparin-binding growth factor, is expressed in neural precursor cells and promotes their growth. Reviewed

    Zou, P., Muramatsu, H., Miyata, T., and Muramatsu, T

    J. Neurochem   Vol. 99   page: 1470-1479   2006

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  94. 神経上皮における細胞周期,運命決定,組織形成運動のリンク Invited

    宮田卓樹

    実験医学   Vol. 23   page: 1480-1485   2005

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  95. スライス培養により読み解く中枢神経系の組織形成機構 Invited

    宮田卓樹

    日本神経精神薬理雑誌   Vol. 25   page: 175-181   2005

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  96. 「脳室下帯」における皮質ニューロン産生 Invited

    宮田卓樹

    脳21   Vol. 8   page: 245-250   2005

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  97. Modern slice culture for direct observation of production and migration of brain neurons Reviewed

    Miyata T, Saito K, Nishizawa Y, Murayama A, Masaoka M, Ogawa M.

    Nagoya J Med Sci   Vol. 67   page: 65-70   2005

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  98. Physiological function of S-cone system is not enhanced in rd7 mice. Reviewed

    Ueno S, Kondo M, Miyata K, Hirai T, Miyata T, Usukura J, Nishizawa Y, Miyake Y.

    Exp Eye Res.   ( 81 ) page: 751-758   2005

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    DOI: 10.1016/j.exer.2005.04.013

  99. Both type-I hemidesmosomes and adherens-type junctions contribute to the cell-substratum adhesion system in myoepithelial cells. Reviewed

    Uematsu J, Nishizawa Y, Hirako Y, Kitamura K, Usukura J, Miyata T, Owaribe K.

    Eur J Cell Biol.   ( 84 ) page: 407-415   2005

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    DOI: 10.1016/j.ejcb.2005.01.001

  100. Differential expression of Pax6 and Ngn2 between pair-generated cortical neurons. Reviewed

    Kawaguchi, A., Ogawa, M., Saito, K., Matsuzaki, F., Okano, H., and Miyata, T.

    J. Neurosci. Res.   Vol. 78   page: 784-795   2004

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  101. 小脳の縦縞状区画化と皮質形成:Purkinje細胞の誕生・移動・配置の分子機構 Invited

    橋本光広,宮田卓樹

    脳の科学   Vol. 25   page: 543-549   2003

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  102. Morphological asymmetry in dividing retinal progenitor cells. Reviewed

    Saito, K., Kawaguchi, A., Kashiwagi, S., Yasugi, S., Ogawa, M., and Miyata, T.

    Develop. Growth & Differ.   Vol. 45   page: 219-229   2003

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  103. Differential expression of Musashi1 and nestin in the adult rat hippocampus after ischemia. Reviewed

    Yagita Y, Kitagawa K, Sasaki T, Miyata, T., Okano H, Hori M, Matsumoto M. Differential

    J. Neurosci. Res.   Vol. 69   page: 750-756   2002

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  104. 胎生期大脳組織の三次元培養:複雑さへの回帰 Invited

    宮田卓樹,齋藤加奈子,川口綾乃,小川正晴

    生体の科学   Vol. 53   page: 243-249   2002

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  105. Absence of Cajal-Retzius cells and subplate neurons associated with defects of tangential migration from ganglionic eminence in Emx1/2 double mutant cerebral cortex. Reviewed

    Shinozaki, K., Miyagi, T., Yoshida, M., Miyata, T., Ogawa, M., Aizawa, S., and Suda, Y.

    Development   Vol. 129   page: 3479-3492   2002

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  106. Visualization of cell cycling by an improvement in slice culture methods. Reviewed

    Miyata, T., Kawaguchi, A., Saito, K., Kuramochi, H., and Ogawa, M.

    J. Neurosci. Res.   Vol. 69   page: 861-868   2002

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  107. Transplantation of in vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult rats. Reviewed

    Ogawa Y, Sawamoto K, Miyata,T., Miyao S, Watanabe M, Nakamura M, Bregman BS, Koike M, Uchiyama Y, Toyama Y, Okano H.

    J. Neurosci. Res.   Vol. 69   page: 925-933   2002

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  108. Increased proliferation of neural progenitor cells but reduced survival of newborn cells in the contralateral hippocampus after focal cerebral ischemia in rats. Reviewed

    Takasawa K, Kitagawa K, Yagita Y, Sasaki T, Tanaka S, Matsushita K, Ohstuki T, Miyata T, Okano H, Hori M, Matsumoto M.

    J. Cereb. Blood Flow Metab.   Vol. 22   page: 299-307   2002

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  109. Proliferation of neuronal progenitor cells and increased neurogenesis in the ischemic adult rat hippocampus. Reviewed

    Yagita, Y., Kitagawa, K., Otsuki, T., Kuwabara, K., Mabuchi, T., Miyata, T., Okano, H., Hori, M., and Matsumoto, M.:

    Stroke   Vol. 32   page: 1890-1896   2001

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  110. Assessment of the developmental totipotency of neural cells in the cerebral cortex of mouse embryo by nuclear transfer. Reviewed

    Yamazaki, Y., Makino, H., Hamaguchi-Hamada, K., Hamada, S., Sugino, H., Kawase, E., Miyata, T., Ogawa, M., Yanagimachi. R., and Yagi, T.

    Proc. Natl. Acad. Sci. USA   Vol. 98   page: 14022-14026   2001

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  111. Nestin-EGFP mice: visualization of the self-renewal and multipotency of CNS stem cells. Reviewed

    Kawaguchi, A., Miyata, T., Sawamoto, K., Takashita, N., Murayama, A., Akamatsu, W., Ogawa, M., Okabe, M., Tano, Y., Goldman, S.A., and Okano, H.

    Mol. Cell. Neurosci.   Vol. 17   page: 259-273   2001

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  112. 大脳皮質におけるニューロンの産生と配置の機構 Invited

    宮田卓樹,小川正晴

    医学のあゆみ   Vol. 199   page: 1000-1004   2001

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    Authorship:Lead author   Language:Japanese   Publishing type:Research paper (scientific journal)  

  113. 発達脳における神経細胞の移動: 新しいニューロン移動法とその原理 Invited

    宮田卓樹,川口綾乃,岡野栄之,小川正晴

    生体の科学   Vol. 52   page: 224-229   2001

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  114. DiI を用いた脳原基スライス培養ー神経上皮ジャングル探検の愉しみー Invited

    宮田卓樹

    細胞工学   Vol. 20   page: 1410-1419   2001

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  115. Musashi1: an evolutionally conserved marker for CNS progenitor cells including neural stem cells. Reviewed

    Kaneko, Y., Sakakibara, S., Imai, T., Suzuki, A., Nakamura, Y., Sawamoto, K., Ogawa, Y., Toyama, Y., Miyata, T., and Okano, H.

    Dev. Neurosci.   Vol. 22   page: 139-153   2000

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  116. The bHLH gene Hes1 as a repressor of neuronal commitment of the CNS stem cells. Reviewed

    Nakamura, Y., Sakakibara, S., Miyata, T., Ogawa, M., Shimazaki, T., Weiss, S., Kageyama, R., and Okano, H.

    J. Neurosci.   Vol. 20   page: 283-293   2000

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  117. Dissection of signaling cascade through gp130 in vivo: Reciprocal roles for STAT3-and SHP2-mediated signals in cytokine and immunoglobulin production. Reviewed

    Ohtani, T., Ishihara, K., Atsumi, T., Nishida, K., Keneko, Y., Miyata, T., Itoh, S., Narimatsu, M., Maeda, H., Fukada, T., Itoh, M., Okano, H., Hibi, T., and Hirano, T.

    Immunity   Vol. 12   page: 95-105   2000

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  118. 小脳の発生に関する分子機構:プルキンエ細胞と顆粒神経細胞の大河ドラマ Invited

    宮田卓樹,小川正晴

    神経研究の進歩   Vol. 44   page: 965-973   2000

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  119. Distinct arrangement patterns of Purkinje cells between normal and reeler mice are reproduced in cerebellar explants. Reviewed

    Miyata, T., Nakajima, K., Mikoshiba, K., and Ogawa, M.

    Dev. Neurosci.   Vol. 19   page: 124   1997

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  120. A novel neurological mutant mouse, yotari, which exhibits reeler-like phenotype but expresses CR-50 antigen/Reelin. Reviewed

    Yoneshima, H., Nagata, E., Matsumoto, M., Yamada, M., Nakajima, K., Miyata, T., Ogawa, M., and Mikoshiba, K.

    Neurosci. Res.   Vol. 29   page: 217-223   1997

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  121. 大脳・小脳における層形成機構ー「皮質ニューロン号」の離着陸 Invited

    宮田卓樹,仲嶋一範,御子柴克彦,小川正晴

    実験医学   Vol. 15   page: 1600-1606   1997

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  122. A role for Cajal-Retzius cells and reelin in the development of hippocampal connections. Reviewed

    Del Rio, J., Heimrich, B., Borrell, V., Froster, E., Drakew, A., Alcantara, S., Nakajima, K., Miyata, T., Ogawa, M., Mikoshiba, K., Derer, P., Frotscher, M., and Soriano, E.:

    Nature   Vol. 385   page: 70-74   1997

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  123. Disruption of hippocampal development in vivo by CR-50 mAb against Reelin. Reviewed

    Nakajima, K., Mikoshiba, K., Miyata, T., Kudo, C., and Ogawa, M.

    Proc. Natl. Acad. Sci. USA   Vol. 94   page: 8196-8201   1997

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  124. A truncated Reelin protein is produced but not secreted in the 'Orleans' reeler mutation. Reviewed

    De Vergeyck, V., Nakajima, K., Lambert de Rouvroit, C., Naerhuyzen, B., Goffinet, A. M., Miyata, T., Ogawa, M., and Mikoshiba, K.

    Mol. Brain Res.   Vol. 50   page: 85-90   1997

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  125. Reelin is a secreted glycoprotein recognized by the CR-50 monoclonal antibody. Reviewed

    D'Arcangelo, G., Nakajima, K., Miyata, T., Ogawa, M., Mikoshiba, K., Curran, T.

    J. Neurosci.   Vol. 17   page: 23-31   1997

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  126. Mouse-musashi-1, a neural RNA-binding protein highly enriched in the mammalian CNS stem cell. Reviewed

    Sakakibara, S., Okano, H., Imai, T., Hamaguchi, K., Aruga, J., Nakajima, K., Nagata, T., Kurihara, Y., Uesugi, S., Miyata, T., Ogawa, M., and Mikoshiba, K.

    Dev. Biol.   Vol. 176   page: 230-242   1996

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  127. Distribution of a reeler gene-related antigen in the developing cerebellum: an immunohistochemical study with an allogeneic antibody CR-50 on normal and reeler mice. Reviewed

    Miyata, T., Nakajima, K., Aruga, J., Takahashi, S., Ikenaka, K., Mikoshiba, K, and Ogawa, M.

    J Comp. Neurol.   Vol. 372   page: 215-228   1996

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  128. The reeler gene-associated antigen on Cajal-Retzius neurons is a crucial molecule for laminar organization of cortical neurons. Reviewed

    Ogawa, M., Miyata, T., Nakajima, K., Yagyu, K., Ikenaka, K., Yamamoto, H., and Mikoshiba, K.

    Neuron   Vol. 14   page: 899-912   1995

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  129. Identification of two highly homologous presynaptic proteins distinctly localized at the dendritic and somatic synapses. Reviewed

    Takahashi, S., Yamamoto, H., Matsuda, Z., Ogawa, M., Yagyu, K., Taniguchi, T., Miyata, T., Koda, H., Higuchi, T., Okutani, F., and Fujimoto, S.

    FEBS letters   Vol. 368   page: 455-460   1995

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  130. Developmental potentials of early telencephalic neuroepithelial cells: a study with microexplant culture. Reviewed

    Miyata, T., and Ogawa, M.

    Dev. Growth & Differ.   Vol. 36   page: 319-331   1994

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Books 8

  1. 脳の発生学 ニューロンの誕生・分化・回路形成

    宮田卓樹, 山本亘彦( Role: Contributor)

    科学同人  2013 

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    Total pages:280   Language:Japanese Book type:Textbook, survey, introduction

  2. 神経系発生過程における細胞移動(「再生医療叢書 7 神経系」)

    宮田卓樹( Role: Joint author)

    朝倉書店  2013 

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    Total pages:208   Language:Japanese Book type:Scholarly book

  3. 大脳皮質の形成機構 (「脳の発生と発達」岡本 仁 編,シリーズ脳科学4)

    宮田卓樹( Role: Joint author)

    東京大学出版会  2008 

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    Language:Japanese

  4. Asymmetric cell division during brain morphogenesis. (Macieira-Coelho Ed.: Progress in Molecular and Subcellular Biology)

    Miyata, T.( Role: Sole author)

    Springer-verlag  2007 

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    Language:English

  5. 大脳皮質形成という名の「機織り」: タテ糸とヨコ糸の謎 「脳・神経研究のフロンティア」

    宮田卓樹, 小川正晴( Role: Joint author)

    羊土社  2002 

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    Language:Japanese

  6. スライス培養による脳原基のタイムラプス断面視 「図・写真で観る発生・再生実験マニュアル」

    齋藤加奈子,川口綾乃,倉持浩,小川正晴,宮田卓樹( Role: Joint author)

    メディカル・ドウ  2002 

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    Language:Japanese

  7. ニューロン移動・配置と脳の構築化 「みる見るわかる脳・神経科学入門講座」

    宮田卓樹( Role: Joint author)

    羊土社  2002 

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    Language:Japanese

  8. 初期胚からの神経組織培養 ニューロサイエンスラボマニュアル「神経細胞培養法」

    宮田卓樹,小川正晴( Role: Joint author)

    シュプリンガーフェアラーク東京  1997 

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    Language:Japanese

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Presentations 4

  1. Pushing and pulling in the developing brain wall Invited International conference

    Takaki Miyata

    25th Biennial Meeting of the International Society for Developmental Neuroscience (ISDN 2024)  2024.9.24  the International Society for Developmental Neuroscience

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    Event date: 2024.9

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Venue:Montpellier   Country:France  

  2. Contractility in the brain morphogenesis Invited International conference

    Takaki Miyata

    The 52th Naito Conferance: Frontiers of Physical and Mechanical Biology  2024.10.2  The Naito Foundation

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    Event date: 2024.10

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Venue:Sapporo   Country:Japan  

    Other Link: https://www.naito-f.or.jp/en/conference/co_index.php?data=date

  3. 動物の大脳というドーム構造の建築工法 Invited

    宮田卓樹

    日本建築学会  2022.9.8 

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    Event date: 2022.9

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  4. 脳の成長的建築:密に詰まった細胞たちによるセンシングとアクチュエーション Invited

    宮田卓樹

    第63回日本植物生理学会  2022.3.22 

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    Event date: 2022.3

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

Research Project for Joint Research, Competitive Funding, etc. 8

  1. 大規模な細胞産生を支える組織内物流:力学的共生による経済性

    2017.10 - 2018.9

    三菱財団自然科学研究助成金 

    宮田 卓樹

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    Grant type:Competitive

  2. 胎生期小脳における細胞挙動と分子機構

    2009.6

    ブレインサイエンス振興財団 

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    Grant type:Competitive

  3. 胎生期小脳におけるニューロンの誕生・移動・配置に関する研究

    2009.4

    ライフサイエンス振興財団 

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    Grant type:Competitive

  4. 脳形成原理についての多次元的研究:先天性脳奇形の病因解明と治療をめざして

    2008.3

    上原記念生命科学財団 

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    Grant type:Competitive

  5. Piwiファミリー遺伝子の神経幹細胞における役割

    2006.11 - 2008.10

    豊秋奨学会 

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    Grant type:Competitive

  6. ガン転移・上皮間葉転換との共通性に着目したニューロン移動開始機構の研究

    2006.9 - 2008.3

    武田科学振興財団 

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    Grant type:Competitive

  7. 各種三次元培養を用いた脳・網膜組織の極性形成と細胞構築機構に関する研究

    2004.11 - 2005.11

    住友財団 

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    Grant type:Competitive

  8. 脳形成過程における三次元的細胞挙動の観察と原理探求

    2003.11 - 2008.3

    CREST (JST) 

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    Grant type:Competitive

    CRESTの「生物の発生・分化・再生」の平成14年度採択プログラムである「脳構築の遺伝的プログラム」の分担チームの一つとして参加.

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KAKENHI (Grants-in-Aid for Scientific Research) 15

  1. 脳周囲と脳室のフィジカルな協働が大脳発生に果たす役割

    Grant number:24K02205  2024.4 - 2027.3

    基盤研究(B)

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    Authorship:Principal investigator  Grant type:Competitive

  2. 外圧に抗し肥厚成長する脳原基の壁強化工法:蓄エネ的自縛充満と根張りスペーシング

    Grant number:23H04306  2023.4 - 2025.3

    学術変革領域A(公募研究)

  3. Mechanics of brain development: elasticity, residual tissue stress, and mechanosensing

    Grant number:21H02656  2021.4 - 2024.3

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

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    Authorship:Principal investigator 

    Grant amount:\17420000 ( Direct Cost: \13400000 、 Indirect Cost:\4020000 )

  4. Comparative architectonics of hollow fruits and embryonic brains: intramural assembly of tensile and compression materials

    Grant number:21H00363  2021.4 - 2023.3

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

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    Authorship:Principal investigator 

    Grant amount:\1300000 ( Direct Cost: \1000000 、 Indirect Cost:\300000 )

  5. 脳室帯のシステム科学的研究

    2016.4 - 2020.3

    科学研究費補助金  基盤研究(A)

    宮田 卓樹

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    Authorship:Principal investigator 

  6. 母体状態・薬剤の胎生期細胞周期への影響:子宮内ライブ観察から生後評価まで

    2023.4 - 2025.3

    挑戦的研究(萌芽)

  7. 母体状態・薬剤が胎生期器官の細胞周期に及ぼす影響:子宮内ライブ評価系の構築

    Grant number:19K22683  2019.6 - 2021.3

    挑戦的研究(萌芽)

    宮田 卓樹

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\6500000 ( Direct Cost: \5000000 、 Indirect Cost:\1500000 )

    「母体状態・薬剤が胎生期器官の細胞周期に及ぼす影響:子宮内ライブ評価系の構築」は,器官形成期に,ヒト胎児の種々の組織内で進行する細胞周期に対して母体の全身状態の急性変化や薬剤がどのような影響を及ぼしうるかに関して,産婦人科学はもとより,幅広い医学領域にとって有用となる全く新しい知見を得ることをめざし,マウスを用いた鋭敏な評価系を開発する.
    本研究「母体状態・薬剤が胎生期器官の細胞周期に及ぼす影響:子宮内ライブ評価系の構築」は,器官形成期に,ヒト胎児の種々の組織内で進行する細胞周期に対して母体の全身状態の急性変化や薬剤がどのような影響を及ぼしうるかに関して,産婦人科学はもとより,幅広い医学領域にとって有用となる全く新しい知見を得ることをめざしている.
    初年度,マウスを用いた鋭敏な評価系を開発するべく,まず,名古屋大学において細胞周期インディケータであるFucciマウスを用いた観察から着手し,一定の成果をあげた.次いで,基礎生物学研究所(岡崎市)に出向き,全細胞の核・分裂期細胞の染色体の観察を可能とするH2B-EGFPマウスの現地供与のもと,大学共同利用のために備わる二光子顕微鏡観察の支援を受けた.その結果,名古屋大学から持参した手製デバイス一式を用いて,母マウス麻酔,子宮・胎仔の保持のうえ,大脳皮質原基の外表面(脳膜面)から奥に0.25 mm程度まで良好な視野を得ることができた.そして神経幹細胞が脳室面で分裂する様子を,世界で初めて子宮内ライブ観察することに成功した.また分裂の前後の核・細胞体の移動もとらえることができた.視野揺動,胎仔生存等の問題のため連続観察時間が1時間未満に限られるケースが多かった部分は技術的な限界,今後の課題として示されたが,細胞周期インディケータマウスを用いた名古屋大学における観察の結果とあわせて,ここまでに得られた成果は,Development, Growth & Differentiation誌(62巻,118-128頁,2020年)に発表した.哺乳類の発生研究の分野における挑戦の一歩を確かに示すことができた.
    出生後まで細胞産生がつづく多くの器官と異なり,大脳を初めとする脳領域では,細胞づくりが胎生期に限られる.本来の「制限時間」のうちに確実に充分な細胞を生み出せないと,ニューロンの数的・質的な確保が叶わず,生後の脳機能に悪影響がでる恐れがある.細胞周期は,妊娠初期~中期の妊婦に対する薬剤の選択および開発にとって,慎重に副作用評価が行われるべき対象である.従来は,機能的評価が動物モデルを使って行なわれる場合は(1)当該区域における総細胞数や分裂像,あるいは PCNAやKi67などを発現する細胞の数をカウントする,(2)ブロモデオキシウリジン(BrdU)などチミジンアナログの取り込みにもとづくS期の検出など,いずれも,フォルマリン等による固定処置後に,組織の切片に対する所定の化学的染色を経てなされてきた.じつは,これでは,母体状態の“急変”や薬剤投与“直後”の細胞周期応答を鋭敏に知ることはできない.そのため,こうした従来手法で「陰性」判定された胎生期擾乱が,短時間の中断や遅滞など,軽度な細胞周期異常を引き起こす可能性は,じつは否定できない状況にある.したがって,生後の高次脳機能を担う精緻な回路構築の基盤としての胎生期細胞周期に対して,先端手法を駆使して,高時間分解能の(鋭敏な)評価系を開発する必要がある.本研究は,子宮内のマウス胎仔の脳原基に存在する神経幹細胞の分裂をとらえることを目指し,全細胞の核を可視化できるトランスジェニックマウスを用いて1~2時間程度のライブ観察を達成し,分裂頻度を定量化できた.また,細胞周期インディケータFucciマウスを利用することで,細胞周期進行およびそれに付随する核移動を子宮内観察することもできた.これらはいずれも世界初である.
    神経幹細胞によるDNA複製の開始(S期への進入=増殖の決断・意思表示)の頻度や空間分布を定量する. S期完了(G2期の開始=分裂へのゴーサインの一つ)のタイミングも把握する(緑色蛍光の高まりをモニタするとともに,G2に入ると幹細胞が核を脳室方向へ動かし始めることを利用し「緑色の核の動き去り」をとらえるなど,初年度以上に詳細な観察をめざす.次いで,母マウスに対する各種擾乱(酸素,血圧,血糖,体温など全身状況の急変や,薬剤投与)が胎仔内の細胞周期動態にどのような変化(S期開始頻度の低下,すなわち「増殖」でなく「分化」の決断が増えてしまう,あるいは S期進行が遅れるなど)をもたらすか,明らかにする.初年度の予備的な観察で血流障害による虚血すなわち局所低酸素が幹細胞の挙動に影響を与える感触が得られつつあるので,この視点での解析を充実させる.薬剤に対する解析では,以前から胎児毒性や催奇形性が指摘され相対的禁忌とされる薬剤の影響をまず把握し,次いで,別の(比較的安全とみなされてきた)薬剤の影響を調べる.加えて,初年度に,神経幹細胞に対する子宮内観察と平行して行った「脳原基中のミクログリア挙動」についての観察にも一定程度の進捗が見られたので,2年目はこれについても実施を重ね,虚血ほかの負かに対するミクログリア反応をとらえるなどをめざす.そして,神経幹細胞のふるまいに対するミクログリアの関与についても観察する.

  8. 動く細胞と場のクロストークによる秩序の生成

    2010.7 - 2015.3

    科学研究費補助金  新学術領域研究,課題番号:22111001

    宮田 卓樹

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  9. 哺乳類胎仔の in vivo ライブ観察系の確立

    2016.4 - 2018.3

    科学研究費補助金  挑戦的萌芽研究、課題番号:16K15169

    宮田 卓樹

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  10. 動く細胞と場のクロストークによる秩序の生成

    2010.7 - 2015.3

    科学研究費補助金  新学術領域研究,課題番号:22111001

    宮田 卓樹

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  11. 神経前駆細胞の動と静を制御する場と集団の原理

    2010.7 - 2015.3

    科学研究費補助金  新学術領域研究,課題番号:22111006

    宮田 卓樹

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    「神経前駆細胞の動と静を制御する場と集団の原理」は,当領域「動く細胞と場のクロストークによる秩序の生成」の項目A03「組織から器官へ」に属し,1. 脳・脊髄・網膜の基礎となる三次元構造「神経上皮」が,ageや分化度の異なる細胞をいかに自身の中に共存させているか,2. 神経上皮中において,ヘテロな細胞たちの動きがいかに組み合わされ,細胞間の関係性がどう変化していくのか,3. 細胞の動きに裏打ちされた「関係性の変化・ゆらぎ」が,集団としての三次元構造および細胞産生力の維持・変化にどう貢献するのか,を明らかにすることを目指している.H25年度には,本領域発足後に立ち上げた「全細胞のイメージング」をもとにした核移動のトラッキング,子宮内エレクトロポレーションによる機能実験,力学的な実験,シミュレーションなどを組み合わせることにより,神経前駆細胞の集団としての動きには個々の細胞が長く伸びた形態をとることが重要であると明らかにし,また,神経前駆細胞が過剰混雑という力学的負荷を感知して「脱上皮化」という反応を示すことを見いだした(Nature Neuroscience誌に論文出版).この成果は,先天性疾患の病因解明や大脳進化の理解のための基礎的知見として意義を有するとの解説を交えて新聞紙上や各種ウェブサイトで紹介された.一方,細胞動態の解析を通じて,大脳発生に関しての複数の論文の出版に至った(Journal of Neuroscience, Nature Communications, Neuron).

  12. 小脳発生の研究:胎生期のニューロン誕生・移動の機構

    2009.4 - 2013.3

    科学研究費補助金  基盤研究(A),課題番号:21240027

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    本研究は,従来不明な点の多かった胎生期の小脳の形成過程について理解を深めることをめざした.求める基礎的知見が先天性疾患の病態解明や再生医療にむけた取り組みに役立つ事を念頭に,ニューロンと神経前駆細胞の挙動に焦点をあてて研究が行われた.ヒト小脳形成に重要と知られる細胞外因子「リーリン」が移動中の幼若なプルキンエ細胞に対してどういう働きかけをしているかをスライス培養下のライブ観察などによって明らかにした.また,プルキンエ細胞を産生する神経前駆細胞の細胞周期動態,分裂の様式を明らかにした.
    This study aimed at elucidating mechanisms of cerebellar development. Special attentions were paid on the behavior of young Purkinje cells and their progenitor cells. Understanding of how Purkinje cells migrate and form a layer in the cerebellar cortex is important for dissecting pathogenesis of human cerebellar malformations. We visualized newly-generated Purkinje cells’ morphology and dynamics for the first time and the results were published. Cell cycle parameters and lineage of progenitor cells that give rise to Purkinje cells were also studied.

  13. 生体内観察のための哺乳類胎仔灌流保育系の開発

    2009.4 - 2011.3

    科学研究費補助金  基盤研究(A),課題番号:21657056

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    昨今,各種幹細胞を用いて器官の再生・人工的形成を目指そうとする努力が進められている.その成功のためには,まず,本来の組織・器官の形成の原理を深く知る必要がある.立体的な形態形成の原理を解明するためには,生体内の三次元組織における細胞動態をリアルタイムで観察できる手法が必要である.そうしたインビボイメージングの手法は,セブラフィッシュやその他の動物では可能となっているが、哺乳類ではこれまで行なわれたことがない.代わりに,哺乳類では,胎仔の各所から切り出してきた組織を培養することで,生体に準じた環境下での組織の三次元的生育と細胞の挙動の解析とが果たされてきた.しかし,数百ミクロンもの厚みを有する培養スライスに対して適切な酸素供給する困難さ,組織・器官の形成過程に積極的な役割を果たすことが知られる血管を欠く点,また,切り出すことによって組織の縦横要素のからみ・細胞の越境性などを失う点,など,単離スライスには種々の限界もある.
    こうした技術的・生物学的な問題を克服し,胎生期哺乳類の器官に対する生体内でのイメージングを行なうために,本研究では当初,子官・胎盤から分離した胎仔を経心臓的に灌流することで発生を維持できるような系を目指すことにした.しかし昨年度までに得た結果から,胎仔の生育を十分でないケースが多いことが明らかになったので,今年度は,当初抱いた方針とは異なるが同じ目的のために,胎盤で母体(子宮)とつなげたままで胎仔の生育を目指した.これまでに母体の麻酔,全身管理,胎盤周辺の処理,胎膜関連の注意点等が浮き彫りになってきた.また,胎仔の組織と顕微鏡レンズとの接し方をどう適切にとるかについてもノウハウが蓄積されてきた.よって,こうした成果を生かして3次元的なインビボイメージングの具体的な実施を計画できるところまで到達している.本研究を通じて,全く未開拓であった手法の開発を一定のレベルにまで進めることができた.さらなる大規模なプロジェクトの基礎となる貴重なデータを取得することができた.

  14. 遠隔投射型大脳皮質ニューロンの発生と回路形成

    2008.4 - 2010.3

    科学研究費補助金  特定領域研究,課題番号:20021016

    宮田 卓樹

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    大脳皮質における神経回路の形成過程について研究することは,成体の脳活動の原理を知るため,てんかんなどの疾患の病因の理解のために重要であり,かつ,胎生期また出生後の児の生育が組織構築にどう影響するかを知るためにも重要である.大脳皮質ニューロンには役割の違う複数種のニューロンが存在するが,脳幹や脊髄など遠隔地へ投射するニューロンについては,発生と回路形成の機構についての研究がこれまで手薄であった.本研究ではその問題に取り組み,21年度は2つの項目について以下のような成果を得た.
    (1) 大脳皮質の作り主である神経前駆細胞の核移動にRacが関与していることが分かった.前駆細胞は細胞周期進行に随伴して核を移動させることが知られているがその機構はまだよく分かってはいなかった.本研究によって,その一端が明らかになった.今後,核移動の原理をさらに詳しく調べるうえで,また,細胞間相互作用の具体的な様子・意義を研究するための足場を築くことができた.この成果は論文発表した.
    (2) ニューロンが移動をどのように終え,層を築くのか,移動と配置の移行の局面についてこれまでほとんど分かっていなかったが,本研究でのライブ観察によって,活発な形態変化と極性化を通じてこの局面が営まれていることが分かってきた.これまで三次元的には捉えにくかった樹状突起および軸索の形成過程も観察できるようになった.この成果は,海外のものを含むいくつかの学会で発表し,論文作成中である.
    また,ドイツのグループとの共同研究により,大脳発生に関する論文発表に至った.

  15. 神経前駆細胞の細胞周期進行と娘細胞運命決定の時間関係をスライス培養下に探査する

    2004.6 - 2006.3

    科学研究費補助金  特定領域研究,課題番号:16026249

    宮田 卓樹

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    胎生13-14日マウス大脳皮質原基をモデルシステムとして,細胞周期進行と細胞運命決定と細胞運動のリンクに関する以下のような知見を得た.大脳皮質原基(大脳壁と称され,0.2-0.3mmの厚さを有する)の神経前駆細胞は,原基の内面(脳室面)から外面(脳膜面)までつながって細長い形をしている.脳室面ではお互いにアドヘレンスジャンクションによって連結されており,ちょうどえのき茸あるいはカイワレ大根のような状態で「壁」の支柱としての形態をとっている.前駆細胞の核はDNA合成中には脳室面から離れた場所にある.80%程度の前駆細胞は細胞周期のG2期に核を脳室面に送り,そこでM期を迎える.一方,残りの20%程度の前駆細胞は,DNA合成をする位置よりもさらに深部(脳膜側)においてM期を迎え,分裂する.この,「深部での分裂」は,ほとんどがニューロン2つを作る分裂であり,「脳室面での分裂」がニューロンと前駆細胞を1つずつ,あるいは前駆細胞を2つ作るような分裂であるのとは対照的である.この「ニューロン作り専門的な深部での分裂」にあたって,前駆細胞は,脳室面に保有していたアドヘレンスジャンクションを消失し,あたかも根を抜くようにして「深部」へと移動する.本研究は,bHLH型転写因子であるNeurogepin2タンパクが,一部の前駆細胞において細胞周期のG1期をピークとする発現を示すことと,こうした「深部に向かう」形態変化に対して重要な働きをしていることを突き止めた(Development 131,3133-3145,2004;J Neurosci Res 78,784-795,2004).

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Industrial property rights 1

  1. 組織形成過程における細胞のリアルタイム検出方法

    宮田卓樹

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    Applicant:独立行政法人理化学研究所

    Application no:2000-011623  Date applied:2000.1

    Announcement no:2001-204499 

    Patent/Registration no:3668927  Date registered:2005.4 

    Country of applicant:Domestic  

 

Teaching Experience (On-campus) 5

  1. 人体器官の構造

    2023

  2. 基礎セミナーB

    2023

  3. 基礎医学セミナー

    2023

  4. 医学入門

    2023

  5. 全学教養課程「学問の面白さを知る」

    2020

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    高等研究院初年次教育プログラム

Teaching Experience (Off-campus) 1

  1. 大学院セミナー

    2021.10 Fujita Health University)