Updated on 2025/06/10

写真a

 
Ayano Kawaguchi
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Professor
Position
Professor
Profile

頑強な脳発生に貢献する、神経前駆細胞の運命決定の仕組みに興味を持って研究を行っています。

External link

Degree

  • 博士(医学) ( 大阪大学 )

Research Interests

  • 発生

  • 神経前駆細胞

  • 神経発生

  • 非対称分裂

  • 分化

  • 神経幹細胞

  • 包括脳ネットワーク

Research Areas

  • Life Science / Developmental biology

  • Life Science / Neuroscience-general

  • Life Science / Anatomy and histopathology of nervous system

  • Life Science / Anatomy

Education

  • Osaka University   大学院医学系研究科   博士課程

    1998.4 - 2002.3

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  • Osaka University   医学部   医学科

    1989.4 - 1995.3

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    Country: Japan

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Research History

  • 大阪大学医学系研究科 委託講師(兼任)

    2024.4 - 2025.3

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  • Nagoya University   School of Medicine

    2022.12

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  • Okayama University   学術研究院医歯薬学域 人体構成学分野   Professor

    2022.6

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  • Nagoya University   Graduate School of Medicine   Associate Professor

    2008 - 2022

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  • RIKEN   非対称細胞分裂研究グループ   Researcher

    2002 - 2008

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  • Japan Society for Promotion of Science

    2001 - 2002

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Professional Memberships

Committee Memberships

  • 日本解剖学会   代議員  

    2022.6   

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Papers

  • Surgical training in extraperitoneal laparoscopic para‑aortic lymphadenectomy for the treatment of gynecological cancer using a Thiel‑embalmed cadaver Reviewed

    Shoji Nagao, Masaaki Andou, Kyohei Irie, Kotaro Kubo, Naoyuki Ida, Takaaki Komiyama, Toshiya Kameoka, Ayano Kawaguchi, Hisashi Masuyama

    Oncology Letters   27 ( 6 )   2024.4

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    Publishing type:Research paper (scientific journal)   Publisher:Spandidos Publications  

    DOI: 10.3892/ol.2024.14422

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  • Calcium signals tune AMPK activity and mitochondrial homeostasis in dendrites of developing neurons Reviewed

    Akane Hatsuda, Junko Kurisu, Kazuto Fujishima, Ayano Kawaguchi, Nobuhiko Ohno, Mineko Kengaku

    Development   150 ( 21 )   2023.11

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

    DOI: 10.1242/dev.201930

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  • Advanced Techniques Using In Vivo Electroporation to Study the Molecular Mechanisms of Cerebral Development Disorders Invited Reviewed

    Chen Yang, Atsunori Shitamukai, Shucai Yang, Ayano Kawaguchi

    International Journal of Molecular Sciences   24 ( 18 )   14128 - 14128   2023.9

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

    The mammalian cerebral cortex undergoes a strictly regulated developmental process. Detailed in situ visualizations, imaging of these dynamic processes, and in vivo functional gene studies significantly enhance our understanding of brain development and related disorders. This review introduces basic techniques and recent advancements in in vivo electroporation for investigating the molecular mechanisms underlying cerebral diseases. In utero electroporation (IUE) is extensively used to visualize and modify these processes, including the forced expression of pathological mutants in human diseases; thus, this method can be used to establish animal disease models. The advent of advanced techniques, such as genome editing, including de novo knockout, knock-in, epigenetic editing, and spatiotemporal gene regulation, has further expanded our list of investigative tools. These tools include the iON expression switch for the precise control of timing and copy numbers of exogenous genes and TEMPO for investigating the temporal effects of genes. We also introduce the iGONAD method, an improved genome editing via oviductal nucleic acid delivery approach, as a novel genome-editing technique that has accelerated brain development exploration. These advanced in vivo electroporation methods are expected to provide valuable insights into pathological conditions associated with human brain disorders.

    DOI: 10.3390/ijms241814128

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  • CD206+ macrophages transventricularly infiltrate the early embryonic cerebral wall to differentiate into microglia Reviewed

    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   42 ( 2 )   112092 - 112092   2023.2

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

    DOI: 10.1016/j.celrep.2023.112092

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  • Neuronal delamination and outer radial glia generation in neocortical development Reviewed

    Kawaguchi A

    Frontiers Cell and Developmental Biology   8   623573   2021.2

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  • Transient microglial absence assists postmigratory cortical neurons in proper differentiation. Reviewed International journal

    Yuki Hattori, Yu Naito, Yoji Tsugawa, Shigenori Nonaka, Hiroaki Wake, Takashi Nagasawa, Ayano Kawaguchi, Takaki Miyata

    Nature communications   11 ( 1 )   1631 - 1631   2020.4

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    Language:English  

    In the developing cortex, postmigratory neurons accumulate in the cortical plate (CP) to properly differentiate consolidating subtype identities. Microglia, despite their extensive surveying activity, temporarily disappear from the midembryonic CP. However, the mechanism and significance of this absence are unknown. Here, we show that microglia bidirectionally migrate via attraction by CXCL12 released from the meninges and subventricular zone and thereby exit the midembryonic CP. Upon nonphysiological excessive exposure to microglia in vivo or in vitro, young postmigratory and in vitro-grown CP neurons showed abnormal differentiation with disturbed expression of the subtype-associated transcription factors and genes implicated in functional neuronal maturation. Notably, this effect is primarily attributed to interleukin 6 and type I interferon secreted by microglia. These results suggest that "sanctuarization" from microglia in the midembryonic CP is required for neurons to appropriately fine-tune the expression of molecules needed for proper differentiation, thus securing the establishment of functional cortical circuit.

    DOI: 10.1038/s41467-020-15409-3

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  • 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   10 ( 1 )   2780 - 2780   2019.6

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    Authorship:Corresponding author   Language:English   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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  • Temporal patterning of neocortical progenitor cells: how do they know the right time? Invited Reviewed

    Kawaguchi A

    Neuroscience Research   138   3 - 11   2019.1

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    Authorship:Corresponding author  

    DOI: 10.1016/j.neures.2018.09.004

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

    Kanako Saito, Ryotaro Kawasoe, Hiroshi Sasaki, Ayano Kawaguchi, Takaki Miyata

    Neurochemical Research   43 ( 1 )   171 - 180   2018.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer New York LLC  

    DOI: 10.1007/s11064-017-2390-x

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  • Division modes and physical asymmetry in cerebral cortex progenitors Reviewed

    Delphine Delaunay, Ayano Kawaguchi, Colette Dehay, Fumio Matsuzaki

    CURRENT OPINION IN NEUROBIOLOGY   42   75 - 83   2017.2

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

    DOI: 10.1016/j.conb.2016.11.009

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  • 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   4   139   2016.11

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    Publishing type:Research paper (scientific journal)   Publisher:Frontiers Media SA  

    DOI: 10.3389/fcell.2016.00139

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

    Mayumi Okamoto, Takaki Miyata, Daijiro Konno, Hiroki R. Ueda, Takeya Kasukawa, Mitsuhiro Hashimoto, Fumio Matsuzaki, Ayano Kawaguchi

    NATURE COMMUNICATIONS   7   11349   2016.4

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

    DOI: 10.1038/ncomms11349

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  • Cell cycle-arrested cells know the right time Reviewed

    Ayano Kawaguchi, Fumio Matsuzaki

    CELL CYCLE   15 ( 20 )   2683 - 2684   2016

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    Authorship:Corresponding author   Language:English  

    DOI: 10.1080/15384101.2016.1204857

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

    Takaki Miyata, Mayumi Okamoto, Tomoyasu Shinoda, Ayano Kawaguchi

    FRONTIERS IN CELLULAR NEUROSCIENCE   8   473   2015.1

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

    DOI: 10.3389/fncel.2014.00473

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  • 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   56 ( 4 )   293 - 304   2014.5

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

    DOI: 10.1111/dgd.12131

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

    Mayumi Okamoto, Takashi Namba, Tomoyasu Shinoda, Takefumi Kondo, Tadashi Watanabe, Yasuhiro Inoue, Kosei Takeuchi, Yukiko Enomoto, Kumiko Ota, Kanako Oda, Yoshino Wada, Ken Sagou, Kanako Saito, Akira Sakakibara, Ayano Kawaguchi, Kazunori Nakajima, Taiji Adachi, Toshihiko Fujimori, Masahiro Ueda, Shigeo Hayashi, Kozo Kaibuchi, Takaki Miyata

    NATURE NEUROSCIENCE   16 ( 11 )   1556 - 1566   2013.11

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    DOI: 10.1038/nn.3525

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

    Takaki Miyata, Yuichi Ono, Mayumi Okamoto, Makoto Masaoka, Akira Sakakibara, Ayano Kawaguchi, Mitsuhiro Hashimoto, Masaharu Ogawa

    NEURAL DEVELOPMENT   5   23   2010.9

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

    DOI: 10.1186/1749-8104-5-23

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  • Lunatic fringe potentiates Notch signaling in the developing brain Reviewed

    Tomoaki M. Kato, Ayano Kawaguchi, Yoichi Kosodo, Hitoshi Niwa, Fumio Matsuzaki

    MOLECULAR AND CELLULAR NEUROSCIENCE   45 ( 1 )   12 - 25   2010.9

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    DOI: 10.1016/j.mcn.2010.05.004

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  • Mechanisms that regulate the number of neurons during mouse neocortical development Reviewed

    Takaki Miyata, Daichi Kawaguchi, Ayano Kawaguchi, Yukiko Gotoh

    CURRENT OPINION IN NEUROBIOLOGY   20 ( 1 )   22 - 28   2010.2

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    DOI: 10.1016/j.conb.2010.01.001

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  • Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis Reviewed

    Ayano Kawaguchi, Tomoko Ikawa, Takeya Kasukawa, Hiroki R. Ueda, Kazuki Kurimoto, Mitinori Saitou, Fumio Matsuzaki

    DEVELOPMENT   135 ( 18 )   3113 - 3124   2008.9

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

    DOI: 10.1242/dev.022616

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

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

    JOURNAL OF NEUROSCIENCE RESEARCH   78 ( 6 )   784 - 795   2004.12

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

    DOI: 10.1002/jnr.20347

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

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

    DEVELOPMENT   131 ( 13 )   3133 - 3145   2004.7

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    DOI: 10.1242/dev.01173

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  • Morphological asymmetry in dividing retinal progenitor cells Reviewed

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

    DEVELOPMENT GROWTH & DIFFERENTIATION   45 ( 3 )   219 - 229   2003.6

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    DOI: 10.1046/j.1524-4725.2003.690.x

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  • Flow cytometric analysis of neural stem cells in the developing and adult mouse brain Reviewed

    A Murayama, Y Matsuzaki, A Kawaguchi, T Shimazaki, H Okano

    JOURNAL OF NEUROSCIENCE RESEARCH   69 ( 6 )   837 - 847   2002.9

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    DOI: 10.1002/jnr.10339

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

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

    JOURNAL OF NEUROSCIENCE RESEARCH   69 ( 6 )   861 - 868   2002.9

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    DOI: 10.1002/jnr.10335

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  • Asymmetric inheritance of radial glial fibers by cortical neurons Reviewed

    T Miyata, A Kawaguchi, H Okano, M Ogawa

    NEURON   31 ( 5 )   727 - 741   2001.9

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    DOI: 10.1016/S0896-6273(01)00420-2

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  • Direct isolation of committed neuronal progenitor cells from transgenic mice coexpressing spectrally distinct fluorescent proteins regulated by stage-specific neural promoters Reviewed

    K Sawamoto, A Yamamoto, A Kawaguchi, M Yamaguchi, K Mori, SA Goldman, H Okano

    JOURNAL OF NEUROSCIENCE RESEARCH   65 ( 3 )   220 - 227   2001.8

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    DOI: 10.1002/jnr.1145

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  • In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus Reviewed

    NS Roy, S Wang, L Jiang, J Kang, A Benraiss, C Harrison-Restelli, R Fraser, WT Couldwell, A Kawaguchi, H Okano, M Nedergaard, SA Goldman

    NEUROLOGICAL SURGERY   29 ( 2 )   195 - 195   2001.2

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  • Nestin-EGFP transgenic mice: Visualization of the self-renewal and multipotency of CNS stem cells Reviewed

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

    MOLECULAR AND CELLULAR NEUROSCIENCE   17 ( 2 )   259 - 273   2001.2

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    DOI: 10.1006/mcne.2000.0925

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  • In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus Reviewed

    NS Roy, S Wang, L Jiang, J Kang, A Benraiss, C Harrison-Restelli, RAR Fraser, WT Couldwell, A Kawaguchi, H Okano, M Nedergaard, SA Goldman

    NATURE MEDICINE   6 ( 3 )   271 - 277   2000.3

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

    DOI: 10.1038/73119

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  • Promoter-targeted selection and isolation of neural progenitor cells from the adult human ventricular zone Reviewed

    NS Roy, A Benraiss, S Wang, RAR Fraser, R Goodman, WT Couldwell, M Nedergaard, A Kawaguchi, H Okano, SA Goldman

    JOURNAL OF NEUROSCIENCE RESEARCH   59 ( 3 )   321 - 331   2000.2

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

    DOI: 10.1002/(SICI)1097-4547(20000201)59:3<321::AID-JNR5>3.0.CO;2-9

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MISC

  • Regulation of neural stem cell morphology in brain Invited

    55 ( 10 )   850 - 853   2023.8

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    Authorship:Last author, Corresponding author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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  • Morphological perspectives on the fate determination of neural progenitor cells Invited

    Ayano Kawaguchi

    Journal of Okayama Medical Association   135 ( 1 )   12 - 17   2023.4

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    Authorship:Lead author, Last author, Corresponding author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (bulletin of university, research institution)  

    DOI: 10.4044/joma.135.12

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  • 細胞離脱の実行役分子Lzts1による大脳形成制御 Reviewed

    川口綾乃

    生化学   92 ( 6 )   817 - 821   2020.12

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  • 非対称分裂

    川口綾乃, 松崎文雄

    分子細胞治療   3 ( 1 )   138 - 139   2004

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  • 実験講座 胎生期大脳組織の三次元培養:複雑さへの回帰

    宮田 卓樹, 齋藤 加奈子, 川口 綾乃

    生体の科学   53 ( 3 )   243 - 249   2002.5

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    Language:Japanese   Publisher:金原一郎記念医学医療振興財団  

    DOI: 10.11477/mf.2425902403

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  • 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 (特集 脳の発達に関与する分子機構)

    宮田 卓樹, 川口 綾乃, 岡野 栄之

    生体の科学   52 ( 3 )   224 - 229   2001.5

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    DOI: 10.11477/mf.2425902273

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  • 神経系前駆細胞及び成熟ニューロンの非対称性に関する細胞生物学的解析

    岡野栄之, 飯島崇利, 川口綾乃, 宮田卓樹, 今井貴雄, 小川正晴

    日本分子生物学会年会プログラム・講演要旨集   23rd   292   2000.11

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    Language:Japanese  

    J-GLOBAL

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  • 神経幹細胞の同定--中枢神経系の再生を目指して (特集 幹細胞システムと再生医学)

    川口 綾乃, 岡野 栄之

    細胞工学   19 ( 3 )   392 - 397   2000.3

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    Language:Japanese   Publisher:秀潤社  

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  • FACSを用いた神経系前駆細胞の分離

    川口綾乃, 岡野栄之

    実験医学   18   1106 - 1108   2000

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  • 神経幹細胞の同定とその中枢神経再生への応用の展望

    川口綾乃, 岡野栄之

    最新医学   54   1721 - 1729   1999

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Research Projects

  • 細胞治療のための液性因子作用局所化による人工合成ニッチの開発

    Grant number:24K22406  2024.06 - 2027.03

    日本学術振興会  科学研究費助成事業  挑戦的研究(萌芽)

    川口 綾乃, 下向 敦範

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

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  • 上皮構造からの細胞離脱による器官形成制御

    2022 - 2028

    科学技術振興機構  戦略的な研究開発の推進 創発的研究支援事業 

    川口 綾乃

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    体を構成する各器官が適切な機能を発揮するためには、各器官が作られる発生過程で細胞たちが適切な位置に移動し配置されることが重要です。本研究では、脳の発生を主要なモデルとして、上皮構造から細胞が離脱し移動していく際に働く実行役分子に注目し、その仕組みを明らかにします。得られた成果を利用して、人工的に細胞を動かし、器官形成を制御する技術を得ることを目指します。

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  • 上皮構造からの細胞の離脱・移動の新しい分子制御機構

    2022 - 2023

    上原記念生命科学財団  研究助成金 

    川口綾乃

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  • 異所性灰白質病態と脳進化に関わる脳室下帯の形成メカニズムの解明

    2020 - 2023

    文部科学省  科学研究費補助金 基盤B 

    川口綾乃

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    Authorship:Principal investigator  Grant type:Competitive

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  • 場の変化が明らかにする神経前駆細胞の時間個性獲得の機構

    2019 - 2020

    文部科学省  科学研究費補助金 新学術領域(公募研究) 

    川口綾乃

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    Authorship:Principal investigator  Grant type:Competitive

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  • 大脳皮質の脳回形成に寄与する神経前駆細胞移動の分子機構

    2018

    堀科学芸術振興財団  第27回研究助成 

    川口綾乃

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    Authorship:Principal investigator  Grant type:Competitive

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  • Outer radial glia誕生がもたらす神経幹細胞の場と時間特性の変化

    2017 - 2018

    文部科学省  科学研究費補助金 新学術領域(公募研究) 

    川口綾乃

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    Authorship:Principal investigator  Grant type:Competitive

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  • Systems science for the ventricular zone

    Grant number:16H02457  2016.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    Miyata Takaki

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    Grant amount:\45500000 ( Direct expense: \35000000 、 Indirect expense:\10500000 )

    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.

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  • 大脳発生過程における脳室面からの細胞離脱制御

    2016 - 2019

    文部科学省  科学研究費補助金 基盤C 

    川口綾乃

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    Authorship:Principal investigator  Grant type:Competitive

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  • 神経幹細胞の分化に際し速やかに発現変動する遺伝子の脳組織形成への関与

    2013 - 2016

    文部科学省  科学研究費補助金 基盤C 

    川口綾乃

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  • 発生時期による神経幹細胞の分裂パターンの変化を制御する機構の解明

    2011 - 2012

    文部科学省  科学研究費補助金 新学術領域(公募研究) 

    川口綾乃

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

    Grant number:22111006  2010.04 - 2016.03

    Japan Society for the Promotion of Science  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) 

    Grant amount:\190190000 ( Direct expense: \146300000 、 Indirect expense:\43890000 )

    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.

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  • Studies on the reguratory mechanisms for maintainenance and differentiation of neural stem cells in the developmental brain

    Grant number:22500289  2010 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    KAWAGUCHI Ayano

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    Genome-wide transcriptome profiles of single mouse cortical progenitors identified a set of temporally-regulated genes in embryonic neural stem cells (NSCs). Early NSCs showed cell-to-cell variations of Notch signaling-related gene expression, while later NSDs were more homogenous in Notch signaling status, suggesting a shift of NSC-maintaining strategy. I also found that neither initial oscillatory Notch activation nor cell cycle progression is necessary for NSCs’ internal “clock” mechanisms.

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  • Elucidating mechanisms of embryonic cerebellar development

    Grant number:21240027  2009 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    MIYATA Takaki, KAWAGUCHI Ayano, SAKAKIBARA Akira, HASHIMOTO Mitsuhiro

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    Grant amount:\39910000 ( Direct expense: \30700000 、 Indirect expense:\9210000 )

    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.

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  • 単一細胞マイクロアレイ法を用いた神経前駆細胞の時期特異的な分化制御機構の解析

    2008 - 2010

    名古屋大学学術振興基金  H20年度第2回学術研究助成 

    川口綾乃

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  • 単一細胞遺伝子発現解析法を用いた、ほ乳類中枢神経系の前駆細胞の運命決定因子の探索

    Grant number:18680030  2006 - 2007

    文部科学省  科学研究費補助金 若手(A)  若手研究(A)

    川口綾乃

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    Authorship:Principal investigator  Grant type:Competitive

    本研究の目的は、哺乳類大脳の発生過程において前駆細胞から生じる多様な細胞の運命はどのようにして決定されるのか、その分子機構を、単一細胞レベルで遺伝子発現を比較するという手法を用いて明らかにすることにある。昨年度までに、胎生14日目のマウス大脳原基から無作為に取り出した単一細胞から、単一細胞由来cDNAを作製した。それぞれに対し、DNAマイクロアレイ(GeneChip)を用いて遺伝子発現解析を行い、計70個の細胞のゲノム・ワイドな遺伝子発現プロファイルを作製することができた。今年度は得られたデータの解析と、前駆細胞種に得意的な遺伝子の生体内での発現パターンの解析をさらに進め、(1)胎生中期の前駆細胞群はその遺伝子発現のパターンに基づいて、神経幹細胞、脳室下帯にある成熟した中間前駆細胞、その前段階の、脳室帯に存在する幼弱な中間前駆細胞の3種に分かれることを明らかとし、(2)それぞれに特徴的に発現するマーカー遺伝子群を多数同定した。さらに、得られた遺伝子発現情報のパスウェイ解析と各種機能実験に基づき、(3)生体内では、脳室面側に存在する幼弱な中間前駆細胞がDeltaを発現していること、この中間前駆細胞と神経幹細胞との間でのDelta-Notchシグナルを介したnegative feedback loopが、発生期における神経細胞産生の数とタイミングを制御していることを明らかとした。得られた成果を、横浜で行なわれたNeuro2007にて報告するとともに(口演)、論文としてまとめ学術誌に投稿した。

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  • 哺乳類中枢神経系における非対称分裂を介した細胞運命決定機構の解析

    Grant number:15700264  2003 - 2005

    文部科学省  科学研究費補助金 若手(B)  若手研究(B)

    川口綾乃

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    Authorship:Principal investigator  Grant type:Competitive

    マウス胎生期の大脳に含まれる前駆細胞は、その分裂能から(1)分裂能を持つ前駆細胞と分裂能を失ったニューロンの対を生み出すもの、(2)ニューロンの対を生み出すもの、(3)分裂能を持つ前駆細胞の対を生み出すものの、少なくとも3グループに分類することができる。本研究では、これら対称分裂・非対称分裂を介した細胞の運命決定機構を知るため、単一細胞レベルで遺伝子発現と細胞の運命との相関を調べることを計画した。平成16年度までに、単一の前駆細胞からcDNAを得る手法を確立し、102個の単一細胞由来cDNAを作成した。定量的PCR法によって各種マーカーとなる遺伝子の発現パターンからこれらの細胞をグループとして分類することが可能であった。そこで平成17年度は、30枚のマイクロアレイを用いて、これらの単一細胞由来cDNAにおける遺伝子発現の各グループ間での比較を網羅的に行った。その結果から絞り込んだ遺伝子について、そのmRNAの発現パターンをin situ hybridizationにより検討し、さらに102の単一細胞由来cDNAサンプルでのその発現量を定量的PCR法により測定した。これらの結果から、「ニューロンの対を生み出す前駆細胞」に特異的に発現している遺伝子を9個同定することができた。その中の一つである機能が未知の遺伝子SVZ1について、マウス胎児脳での発現阻害実験を行ったところ、細胞が脳室帯に留まるという表現形が観察され、本遺伝子が細胞の運命決定、移動、あるいはその両方に関わっている可能性が示唆された。

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  • 中枢神経系幹細胞による細胞産生、組織構築のメカニズムの解明

    Grant number:01J01058  2001

    日本学術振興会  特別研究奨励費  特別研究員奨励費

    川口綾乃

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    Authorship:Principal investigator  Grant type:Competitive

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