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

  • 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.

  • CHARGE syndrome modeling using patient-iPSCs reveals defective migration of neural crest cells harboring CHD7 mutations

    Okuno, Hironobu, Mihara, Francois Renault, Ohta, Shigeki, Fukuda, Kimiko, Kurosawa, Kenji, Akamatsu, Wado, Sanosaka, Tsukasa, Kohyama, Jun, Hayashi, Kanehiro, Nakajima, Kazunori, Takahashi, Takao, Wysocka, Joanna, Kosaki, Kenjiro, Okano, Hideyuki

    ELIFE 6 2017.11

    Research paper (scientific journal), Accepted,  ISSN  2050-084X

  • Enhanced expression of Pafah1b1 causes over-migration of cerebral cortical neurons into the marginal zone

    Katayama Kei ichi, Hayashi Kanehiro, Inoue Seika, Sakaguchi Kazushige, Nakajima Kazunori

    Brain Structure and Function    1 - 9 2017.08

    ISSN  1863-2653

     View Summary

    <p>Mutations of PAFAH1B1 cause classical lissencephaly in humans. In addition, duplications and triplications of PAFAH1B1 are found in individuals with intellectual disability and other neurological disorders suggesting that proper brain development is highly sensitive to the PAFAH1B1 dosage. To examine the effect of PAFAH1B1 over-dosage in neural development, especially in migration of neurons and layer formation during cerebral cortical development, we overexpressed Pafah1b1 in migrating neurons in the mouse embryonic cortex using in utero electroporation. Enhanced expression of Pafah1b1 in radially-migrating neurons resulted in their over-migration into the marginal zone. Neurons that invaded the marginal zone were oriented abnormally. Layer distribution of Pafaha1b1-overexpressing neurons shifted more superficially than control neurons. Some of the Pafaha1b1-overexpressing future layer 4 neurons changed their positions to layers 2/3. Furthermore, they also changed their layer marker expression from layer 4 to layers 2/3. These results suggest that overexpression of Pafah1b1 affects the migration of neurons and disrupts layer formation in the developing cerebral cortex, and further support the idea that appropriate dosage of Pafah1b1 is crucial for the proper development of the brain.</p>

  • The brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination

    Hayashi Kanehiro, Furuya Asako, Sakamaki Yuriko, Akagi Takumi, Shinoda Yo, Sadakata Tetsushi, Hashikawa Tsutomu, Shimizu Kazuki, Minami Haruka, Sano Yoshitake, Nakayama Manabu, Furuichi Teiichi

    PLoS ONE 12 ( 3 )  2017.03

    ISSN  1932-6203

     View Summary

    <p>Very-KIND/Kndc1/KIAA1768 (v-KIND) is a brain-specific Ras guanine nucleotide exchange factor carrying two sets of the kinase non-catalytic C-lobe domain (KIND), and is predominantly expressed in cerebellar granule cells. Here, we report the impact of v-KIND deficiency on dendritic and synaptic growth in cerebellar granule cells in v-KIND knockout (KO) mice. Furthermore, we evaluate motor function in these animals. The gross anatomy of the cerebellum, including the cerebellar lobules, layered cerebellar cortex and densely-packed granule cell layer, in KO mice appeared normal, and was similar to wild-type (WT) mice. However, KO mice displayed an overgrowth of cerebellar granule cell dendrites, compared with WT mice, resulting in an increased number of dendrites, dendritic branches and terminals. Immunoreactivity for vGluT2 (a marker for excitatory presynapses of mossy fiber terminals) was increased in the cerebellar glomeruli of KO mice, compared with WT mice. The postsynaptic density around the terminals of mossy fibers was also increased in KO mice. Although there were no significant differences in locomotor ability between KO and WT animals in their home cages or in the open field, young adult KO mice had an increased grip strength and a tendency to exhibit better motor performance in balance-related tests compared with WT animals. Taken together, our results suggest that v-KIND is required for compact dendritic growth and proper excitatory synaptic connections in cerebellar granule cells, which are necessary for normal motor coordination and balance.</p>

display all >>

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

display all >>

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

  • EMBRYOLOGY

    2023

  • ANATOMY AND EMBRYOLOGY 2

    2023

  • ANATOMY

    2023

  • *NEUROANATOMY

    2023

  • *(HEAD AND NECK) ANATOMY AND EMBRYOLOGY

    2023

display all >>

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

display all >>

 

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