Hayashi, Kanehiro

写真a

Affiliation

School of Medicine, Department of Anatomy (Shinanomachi)

Position

Assistant Professor/Senior Assistant Professor

External Links

Academic Background 【 Display / hide

  • 1992.04
    -
    1996.03

    Tokyo Institute of Technology, 生命理工学部, 生命理学科

    University, Graduated

  • 1996.04
    -
    1998.03

    Tokyo Institute of Technology, 生命理工学研究科, バイオサイエンス専攻

    Graduate School, Completed, Master's course

  • 1998.04
    -
    2003.03

    東京大学, 医学系研究科, 脳神経医学

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 医学博士, The University of Tokyo, Coursework, 2003.03

 

Research Areas 【 Display / hide

  • Life Science / Neuroscience-general

  • Life Science / Anatomy and histopathology of nervous system

 

Books 【 Display / hide

  • ‘Reelin’ in Encyclopedia of Signaling Molecules (2nd Edition)

    Hayashi K, Inoue S, Nakajima K, Springer International Publishing, 2018

  • 有芯小胞の分泌制御遺伝子CAPS2と自閉症感受性

    定方哲史, 篠田陽, 林周宏, 古市貞一, 実験医学増刊(羊土社), 2010

  • 自閉症の感受性候補遺伝子と動物モデル.

    篠田陽, 定方哲史, 林周宏, 古市貞一, 脳と精神の医学, 2009

Papers 【 Display / hide

  • Development of intensiometric indicators for visualizing N-cadherin interaction across cells

    Kanadome T., Hayashi K., Seto Y., Eiraku M., Nakajima K., Nagai T., Matsuda T.

    Communications Biology (Communications Biology)  5 ( 1 )  2022.12

     View Summary

    N-cadherin (NCad) is a classical cadherin that mediates cell–cell interactions in a Ca2+-dependent manner. NCad participates in various biological processes, from ontogenesis to higher brain functions, though the visualization of NCad interactions in living cells remains limited. Here, we present intensiometric NCad interaction indicators, named INCIDERs, that utilize dimerization-dependent fluorescent proteins. INCIDERs successfully visualize reversible NCad interactions across cells. Compared to FRET-based indicators, INCIDERs have a ~70-fold higher signal contrast, enabling clear identification of NCad interactions. In primary neuronal cells, NCad interactions are visualized between closely apposed processes. Furthermore, visualization of NCad interaction at cell adhesion sites in dense cell populations is achieved by two-photon microscopy. INCIDERs are useful tools in the spatiotemporal investigation of NCad interactions across cells; future research should evaluate the potential of INCIDERs in mapping complex three-dimensional architectures in multi-cellular systems.

  • Erratic and blood vessel-guided migration of astrocyte progenitors in the cerebral cortex

    Tabata H., Sasaki M., Agetsuma M., Sano H., Hirota Y., Miyajima M., Hayashi K., Honda T., Nishikawa M., Inaguma Y., Ito H., Takebayashi H., Ema M., Ikenaka K., Nabekura J., Nagata K.i., Nakajima K.

    Nature Communications (Nature Communications)  13 ( 1 )  2022.12

     View Summary

    Astrocytes are one of the most abundant cell types in the mammalian brain. They play essential roles in synapse formation, maturation, and elimination. However, how astrocytes migrate into the gray matter to accomplish these processes is poorly understood. Here, we show that, by combinational analyses of in vitro and in vivo time-lapse observations and lineage traces, astrocyte progenitors move rapidly and irregularly within the developing cortex, which we call erratic migration. Astrocyte progenitors also adopt blood vessel-guided migration. These highly motile progenitors are generated in the restricted prenatal stages and differentiate into protoplasmic astrocytes in the gray matter, whereas postnatally generated progenitors do not move extensively and differentiate into fibrous astrocytes in the white matter. We found Cxcr4/7, and integrin β1 regulate the blood vessel-guided migration, and their functional blocking disrupts their positioning. This study provides insight into astrocyte development and may contribute to understanding the pathogenesis caused by their defects.

  • The physiological role of Homer2a and its novel short isoform, Homer2e, in NMDA receptor-mediated apoptosis in cerebellar granule cells

    Furuichi T., Muto Y., Sadakata T., Sato Y., Hayashi K., Shiraishi-Yamaguchi Y., Shinoda Y.

    Molecular Brain (Molecular Brain)  14 ( 1 )  2021.12

     View Summary

    Homer is a postsynaptic scaffold protein, which has long and short isoforms. The long form of Homer consists of an N-terminal target-binding domain and a C-terminal multimerization domain, linking multiple proteins within a complex. The short form of Homer only has the N-terminal domain and likely acts as a dominant negative regulator. Homer2a, one of the long form isoforms of the Homer family, expresses with a transient peak in the early postnatal stage of mouse cerebellar granule cells (CGCs); however, the functions of Homer2a in CGCs are not fully understood yet. In this study, we investigated the physiological roles of Homer2a in CGCs using recombinant adenovirus vectors. Overexpression of the Homer2a N-terminal domain construct, which was made structurally reminiscent with Homer1a, altered NMDAR1 localization, decreased NMDA currents, and promoted the survival of CGCs. These results suggest that the Homer2a N-terminal domain acts as a dominant negative protein to attenuate NMDAR-mediated excitotoxicity. Moreover, we identified a novel short form N-terminal domain-containing Homer2, named Homer2e, which was induced by apoptotic stimulation such as ischemic brain injury. Our study suggests that the long and short forms of Homer2 are involved in apoptosis of CGCs.

  • Both excitatory and inhibitory neurons transiently form clusters at the outermost region of the developing mammalian cerebral neocortex

    Shin M., Kitazawa A., Yoshinaga S., Hayashi K., Hirata Y., Dehay C., Kubo K., Nakajima K.

    Journal of Comparative Neurology (Journal of Comparative Neurology)  527 ( 10 ) 1577 - 1597 2019.07

    ISSN  00219967

     View Summary

    © 2019 Wiley Periodicals, Inc. During development of the mammalian cerebral neocortex, postmitotic excitatory neurons migrate toward the outermost region of the neocortex. We previously reported that this outermost region is composed of densely packed relatively immature neurons; we named this region, which is observed during the late stage of mouse neocortical development, the “primitive cortical zone (PCZ).” Here, we report that postmigratory immature neurons spend about 1–1.5 days in the PCZ. An electron microscopic analysis showed that the neurons in the PCZ tend to be in direct contact with each other, mostly in a radial direction, forming “primitive neuronal clusters” with a height of 3–7 cells and a width of 1–2 cells. A time-course analysis of fluorescently labeled neurons revealed that the neurons took their positions within the primitive clusters in an inside-out manner. The neurons initially participated in the superficial part of the clusters, gradually shifted their relative positions downward, and then left the clusters at the bottom of this structure. GABAergic inhibitory interneurons were also found within the primitive clusters in the developing mouse neocortex, suggesting that some clusters are composed of both excitatory neurons and inhibitory interneurons. Similar clusters were also observed in the outermost region of embryonic day (E) 78 cynomolgus monkey occipital cortex and 23 gestational week (GW) human neocortices. In the primate neocortices, including human, the presumptive primitive clusters seemed to expand in the radial direction more than that observed in mice, which might contribute to the functional integrity of the primate neocortex.

  • Drebrin-like (Dbnl) controls neuronal migration via regulating N-cadherin expression in the developing cerebral cortex

    Inoue S., Hayashi K., Fujita K., Tagawa K., Okazawa H., Kubo K., Nakajima K.

    Journal of Neuroscience (Journal of Neuroscience)  39 ( 4 ) 678 - 691 2019.01

    ISSN  02706474

     View Summary

    © 2019 the authors. The actin cytoskeleton is crucial for neuronal migration in the mammalian developing cerebral cortex. The adaptor protein Drebrin-like (Dbnl) plays important roles in reorganization of the actin cytoskeleton, dendrite formation, and endocytosis by interacting with F-actin, cobl, and dynamin. Although Dbnl is known to be expressed in the brain, the functions of this molecule during brain development are largely unknown. In this study, to examine the roles of Dbnl in the developing cerebral cortex, we conducted experiments using mice of both sexes with knockdown of Dbnl, effected by in utero electroporation, in the migrating neurons of the embryonic cortex. Time-lapse imaging of the Dbnl-knockdown neurons revealed that the presence of Dbnl is a prerequisite for appropriate formation of processes in the multipolar neurons in the multipolar cell accumulation zone or the deep part of the subventricular zone, and for neuronal polarization and entry into the cortical plate. We found that Dbnl knockdown decreased the amount of N-cadherin protein expressed on the plasma membrane of the cortical neurons. The defect in neuronal migration caused by Dbnl knockdown was rescued by moderate overexpression of N-cadherin and αN-catenin or by transfection of the phospho-mimic form(Y337E, Y347E), but not the phospho-resistant form(Y337F, Y347F), of Dbnl. These results suggest that Dbnl controls neuronal migration, neuronal multipolar morphology, and cell polarity in the developing cerebral cortex via regulating N-cadherin expression.

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Papers, etc., Registered in KOARA 【 Display / hide

Presentations 【 Display / hide

  • Analysis of cortical development in a newly established mouse model of extremely preterm infants with brain injuries

    Kubo KI, Deguchi K, Nagai T, Kitazawa A, Yoshida K, Shan W, Aramaki M, Ishii K, Shin MK, Matsunaga Y, Hayashi K, Tanaka KF, Takashima S, Nakayama M, Itoh M, Hirata Y, Antalffy B, Armstrong DD, Yamada K, Inoue K, and Nakajima K

    Neuroscience 2017 meeting, 

    2017.11

    Poster presentation

  • A novel ALS/FTD model mouse expressing cytoplasmic mutant FUS leads neurodegeneration via synaptic disruption

    Shiihashi G, Ito D, Arai I, Kobayashi Y, Hayashi K, Otsuka S, Nakajima K, Yuzaki M, Itohara S, and Suzuki N.

    Neuroscience 2017 meeting, 

    2017.11

    Poster presentation

  • Molecular mechanisms of Reelin-induced neuronal aggregation in the developing mouse neocortex

    Inoue S, Hayashi K, Kubo KI, and Nakajima K

    18th International Congress of Developmental Biology, 

    2017.06

    Poster presentation

  • Novel ALS/FTD model mice expressed cytoplasmic FUS in a toxic gain-of-function manner

    Shiihashi G, Ito D, Kobayashi Y, Itohara S, Hayashi K, Nakajima K, Otsuka S, Yuzaki, M and Suzuki N

    The 13th International Conference on Alzheimer’s and Parkinson’s Diseases, 

    2017.03

    Poster presentation

  • Investigation of the molecular mechanisms underlying Reelin-induced neuronal aggregation in the mouse neocortex

    Inoue S, Hayashi K, Kubo KI, and Nakajima K

    2016 The American Society for Cell Biology (ASCB) Annual Meeting,, 

    2016.12

    Poster presentation

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 発生期にリーリンにより誘導される神経細胞凝集は大脳新皮質層構造の起点となるか?

    2018.04
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • 大脳新皮質層構造形成の礎となる脳表層下における神経細胞集積機構

    2015.04
    -
    2018.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

 

Courses Taught 【 Display / hide

  • HUMAN ANATOMY AND PHYSIOLOGY

    2024

  • EMBRYOLOGY

    2024

  • ANATOMY AND EMBRYOLOGY 2

    2024

  • ANATOMY

    2024

  • *(HEAD AND NECK) ANATOMY AND EMBRYOLOGY

    2023

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Courses Previously Taught 【 Display / hide

  • Neuroanatomy

    Keio University

    2018.04
    -
    2019.03

    Spring Semester, Laboratory work/practical work/exercise, Within own faculty, 120people

    brain, neuron

  • Anatomy

    Keio University

    2018.04
    -
    2019.03

    Autumn Semester, Laboratory work/practical work/exercise, Within own faculty, 120people

  • embryology

    Keio University

    2018.04
    -
    2019.03

    Spring Semester, Lecture, Within own faculty, 120people

  • osteology

    Keio University

    2018.04
    -
    2019.03

    Spring Semester, Laboratory work/practical work/exercise, Within own faculty, 120people

  • 物理化学実習

    武蔵野大学薬学部

    2018.04
    -
    2019.03

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Memberships in Academic Societies 【 Display / hide

  • 日本神経科学学会

     
  • 日本神経化学会

     
  • 日本生化学会

     
  • 日本解剖学会