Updated on 2022/11/01

写真a

 
HATTORI Yuki
 
Organization
Graduate School of Medicine Program in Integrated Medicine Anatomy and Cell Biology Lecturer
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Lecturer
External link

Degree 1

  1. 博士（生命科学） （ 2015.3   京都大学 ） 

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Research Interests 10

  1. ニューロン

  2. glia

  3. microglia

  4. brain development

  5. 細胞移動

  6. neurogenesis

  7. 神経前駆細胞

  8. cerebral cortex

  9. 大脳

  10. ライブイメージング

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Research Areas 2

  1. Life Science / Cell biology

  2. Life Science / Neuroscience-general

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Current Research Project and SDGs 1

  1. 胎生期の脳形成過程におけるミクログリアの動態と機能の解明

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Research History 4

  1. Nagoya University   Lecturer

    2022.6

  2. Nagoya University   Graduate School of Medicine   Designated assistant professor

    2019.8 - 2022.5

  3. Nagoya University   Graduate School of Medicine   Researcher

    2016.4 - 2019.7

  4. Nagoya University   Designated assistant professor

    2015.4 - 2016.3

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Education 2

  1. Kyoto University   Graduate School, Division of Life Science

    2010.4 - 2015.3

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    Country： Japan

  2. Kyoto University   Faculty of Medicine

    2006.4 - 2010.3

    　 More details

    Country： Japan

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Professional Memberships 6

  1. Society for Neuroscience

    2021.9

  2. 日本解剖学会

  3. 日本神経化学会

  4. THE MOLECULAR BIOLOGY SOCIETY OF JAPAN

  5. THE JAPAN NEUROSCIENCE SOCIETY

  6. 日本発生生物学会

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Committee Memberships 1

  1. 日本解剖学会   若手研究者の会　運営委員  

    2022.3   

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    Committee type：Academic society

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Awards 5

  1. 日本解剖学会奨励賞

    2021.3   日本解剖学会   胎生期大脳におけるミクログリア分布の時空間的制御とその生理学的意義

    服部祐季

  2. 医学系研究科医学奨励賞

    2021.2   名古屋大学  

    服部祐季

  3. 第11回NAGOYAグローバルリトリート Best presentation award

    2019.2   名古屋大学大学院医学系研究科  

  4. 第10回NAGOYAグローバルリトリート Best presentation award

    2018.2   名古屋大学大学院医学系研究科  

  5. 第12回国際学生セミナー Outstanding Presentation Award

    2014.2   京都大学大学院生命科学研究科・ウイルス研究所  

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Papers 19

  1. The microglia-blood vessel interactions in the developing brain.

    Hattori Y

    Neuroscience research     2022.9

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    Language：English   Publisher：Neuroscience Research  

    Microglia are the immune cells in the central nervous system (CNS). Once microglial progenitors are generated in the yolk sac, these cells enter the CNS and colonize its structures by migrating and proliferating during development. Although the microglial population in the CNS is still low in this stage compared to adults, these cells can associate with many surrounding cells, such as neural lineage cells and vascular-structure-composing cells, by extending their filopodia and with their broad migration capacity. Previous studies revealed multifaceted microglial actions on neural lineage cells, such as regulating the differentiation of neural progenitors and modulating neuronal positioning. Notably, microglia not only act on neural lineage cells but also interact with blood vessels, for example, by supporting vascular formation and integrity. On the other hand, blood vessels contribute to microglial colonization into the CNS and their migration at local tissues. Importantly, pericytes, the cells that encompass vascular endothelial cells, have been suggested to play a profound role in microglial function. This review summarizes recent advances in the understanding of the interaction of microglia and blood vessels, especially focusing on the significance of this interaction in CNS development, and discusses how microglial and blood vessel dysfunction leads to developmental disorders.

    DOI： 10.1016/j.neures.2022.09.006

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

    Tsujikawa Koyo, Hamanaka Kohei, Riku Yuichi, Hattori Yuki, Hara Norikazu, Iguchi Yohei, Ishigaki Shinsuke, Hashizume Atsushi, Miyatake Satoko, Mitsuhashi Satomi, Miyazaki Yu, Kataoka Mayumi, Li Jiayi, Yasui Keizo, Kuru Satoshi, Koike Haruki, Kobayashi Kenta, Sahara Naruhiko, Ozaki Norio, Yoshida Mari, Kakita Akiyoshi, Saito Yuko, Iwasaki Yasushi, Miyashita Akinori, Iwatsubo Takeshi, Ikeuchi Takeshi, Miyata Takaki, Sobue Gen, Matsumoto Naomichi, Sahashi Kentaro, Katsuno Masahisa

    SCIENCE ADVANCES   Vol. 8 ( 21 ) page： eabm5029   2022.5

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    Language：Japanese   Publisher：Science Advances  

    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

    Web of Science

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

    Hattori Yuki, Itoh Haruka, Tsugawa Yoji, Nishida Yusuke, Kurata Kaori, Uemura Akiyoshi, Miyata Takaki

    JOURNAL OF NEUROSCIENCE   Vol. 42 ( 3 ) page： 362 - 376   2022.1

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    Language：Japanese   Publisher：Journal of 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)b (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 CD11b1 microglia and NG21PDGFRa– 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.

    DOI： 10.1523/JNEUROSCI.1201-21.2021

    Web of Science

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  4. The behavior and functions of embryonic microglia

    Hattori Yuki

    ANATOMICAL SCIENCE INTERNATIONAL   Vol. 97 ( 1 ) page： 1 - 14   2022.1

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    Language：Japanese   Publisher：Anatomical Science International  

    Microglia are the resident immune cells of the central nervous system. Microglial progenitors are generated in the yolk sac during the early embryonic stage. Once microglia enter the brain primordium, these cells colonize the structure through migration and proliferation during brain development. Microglia account for a minor population among the total cells that constitute the developing cortex, but they can associate with many surrounding neural lineage cells by extending their filopodia and through their broad migration capacity. Of note, microglia change their distribution in a stage-dependent manner in the developing brain: microglia are homogenously distributed in the pallium in the early and late embryonic stages, whereas these cells are transiently absent from the cortical plate (CP) from embryonic day (E) 15 to E16 and colonize the ventricular zone (VZ), subventricular zone (SVZ), and intermediate zone (IZ). Previous studies have reported that microglia positioned in the VZ/SVZ/IZ play multiple roles in neural lineage cells, such as regulating neurogenesis, cell survival and neuronal circuit formation. In addition to microglial functions in the zones in which microglia are replenished, these cells indirectly contribute to the proper maturation of post-migratory neurons by exiting the CP during the mid-embryonic stage. Overall, microglial time-dependent distributional changes are necessary to provide particular functions that are required in specific regions. This review summarizes recent advances in the understanding of microglial colonization and multifaceted functions in the developing brain, especially focusing on the embryonic stage, and discuss the molecular mechanisms underlying microglial behaviors.

    DOI： 10.1007/s12565-021-00631-w

    Web of Science

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  5. 胎生期大脳におけるミクログリアの分布調節機構とその意義

    服部 祐季

    ファルマシア   Vol. 58 ( 9 ) page： 868 - 872   2022

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    Language：Japanese   Publisher：公益社団法人 日本薬学会  

    脳には、神経系の細胞の他にも免疫細胞であるミクログリアが存在し、脳の機能を支えている。ミクログリアは胎生期から神経系細胞の分化や配置を制御し、脳発達に貢献していることが明らかにされつつある。胎生期の大脳実質において、ミクログリアは胎齢の進行に伴い分布を変化させる。本稿では、最近筆者らが報告したマウス胎生期の大脳実質内におけるミクログリアの移動メカニズムと、その生理学的意義についての研究内容を中心に紹介する。

    DOI： 10.14894/faruawpsj.58.9_868

    CiNii Research

  6. 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   Vol. 11 ( 1 ) page： 1631 - 1631   2020.4

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

    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

    Web of Science

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

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

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

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

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

    DOI： 10.1111/dgd.12648

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

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

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

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    Publishing type：Research paper (scientific journal)  

  9. Microglia extensively survey the developing cortex via the CXCL12/CXCR4 system to help neural progenitors to acquire differentiated properties. Reviewed International journal

    Hattori Y, Miyata T

    Genes to Cells   Vol. 23 ( 10 ) page： 915 - 922   2018.10

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

    DOI： 10.1111/gtc.12632

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  10. 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. Reviewed International journal

    Hattori Y, Miyata T

    eNeuro   Vol. 5 ( 6 )   2018

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

    DOI： 10.1523/ENEURO.0312-18.2018

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  11. Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown. Reviewed International journal

    Shuntaro Ogura, Kaori Kurata, Yuki Hattori, Hiroshi Takase, Toshina Ishiguro-Oonuma, Yoonha Hwang, Soyeon Ahn, Inwon Park, Wataru Ikeda, Sentaro Kusuhara, Yoko Fukushima, Hiromi Nara, Hideto Sakai, Takashi Fujiwara, Jun Matsushita, Masatsugu Ema, Masanori Hirashima, Takashi Minami, Masabumi Shibuya, Nobuyuki Takakura, Pilhan Kim, Takaki Miyata, Yuichiro Ogura, Akiyoshi Uemura

    JCI insight   Vol. 2 ( 3 ) page： e90905   2017.2

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

    In the central nervous system, endothelial cells (ECs) and pericytes (PCs) of blood vessel walls cooperatively form a physical and chemical barrier to maintain neural homeostasis. However, in diabetic retinopathy (DR), the loss of PCs from vessel walls is assumed to cause breakdown of the blood-retina barrier (BRB) and subsequent vision-threatening vascular dysfunctions. Nonetheless, the lack of adequate DR animal models has precluded disease understanding and drug discovery. Here, by using an anti-PDGFRβ antibody, we show that transient inhibition of the PC recruitment to developing retinal vessels sustained EC-PC dissociations and BRB breakdown in adult mouse retinas, reproducing characteristic features of DR such as hyperpermeability, hypoperfusion, and neoangiogenesis. Notably, PC depletion directly induced inflammatory responses in ECs and perivascular infiltration of macrophages, whereby macrophage-derived VEGF and placental growth factor (PlGF) activated VEGFR1 in macrophages and VEGFR2 in ECs. Moreover, angiopoietin-2 (Angpt2) upregulation and Tie1 downregulation activated FOXO1 in PC-free ECs locally at the leaky aneurysms. This cycle of vessel damage was shut down by simultaneously blocking VEGF, PlGF, and Angpt2, thus restoring the BRB integrity. Together, our model provides new opportunities for identifying the sequential events triggered by PC deficiency, not only in DR, but also in various neurological disorders.

    DOI： 10.1172/jci.insight.90905

    Web of Science

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  12. Glycerol monomycolate is a novel ligand for the human, but not mouse macrophage inducible C-type lectin, Mincle. Reviewed

    Journal of Biological Chemistry   Vol. 289 ( 22 ) page： 15405-15412   2014.5

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

  13. Th1-skewed tissue responses to a mycolyl glycolipid in mycobacteria-infected rhesus macaques. Reviewed

    Morita D, Miyamoto A, Hattori Y, Komori T, Nakamura T, Igarashi T, Harashima H, Sugita M.

    Biochemical and Biophysical Research Communications   Vol. 441 ( 1 ) page： 108-113   2013.11

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

  14. Major T cell response to a mycolyl glycolipid is mediated by CD1c molecules in rhesus macaques. Reviewed

    3) Morita D, Hattori Y, Nakamura T, Igarashi T, Harashima H, Sugita M.

    Infection and Immunity   Vol. 81 ( 1 ) page： 311-316   2013.1

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

  15. GM-CSF-independent CD1a expression in epidermal Langerhans cells: evidence from human CD1A genome-transgenic mice. Reviewed

    4) Kobayashi C, Shiina T, Tokioka A, Hattori Y, Komori T, Kobayashi-Miura M, Takizawa T, Takahara K, Inaba K, Inoko H, Takeya M, Dranoff G, Sugita M.

    Journal of Investigative Dermatology   Vol. 132 ( 1 ) page： 241-244   2012.1

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

  16. 結核菌および抗酸菌の細菌学

    服部祐季, 杉田昌彦

    日本臨床：2011年8月号特集　結核とその類縁疾患〜基礎と臨床の最新知見〜   Vol. 69   page： 1356-1360   2011.8

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    Authorship：Lead author   Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)  

  17. Glycerol monomycolate, a latent tuberculosis-associated mycobacterial lipid, induces eosinophilic hypersensitivity responses in guinea pigs. Reviewed

    Hattori Y, Matsunaga I, Komori T, Urakawa T, Nakamura T, Fujiwara N, Hiromatsu K, Harashima H, Sugita M.

    Biochemical and Biophysical Research Communications   Vol. 409 ( 2 ) page： 304-307   2011.6

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

  18. 結核菌と結核を巡る新たな知見　4. 結核菌細胞壁糖脂質の生合成と免疫認識 Reviewed

    服部祐季, 杉田昌彦

    化学療法の領域   Vol. 27 ( 6 ) page： 1448-1453   2011.5

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

  19. A Microbial Glycolipid Functions as a New Class of Target Antigen for Delayed-type Hypersensitivity. Reviewed

    6) Komori T, Nakamura T, Matsunaga I, Morita D, Hattori Y, Kuwata H, Fujiwara N, Hiromatsu K, Harashima H, Sugita M.

    Journal of Biological Chemistry   Vol. 286 ( 19 ) page： 16800-16806   2011.5

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

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MISC 1

  1. 胎生期大脳におけるミクログリアの分布調節機構とその意義 International journal

    Yuki Hattori

        2020.11

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

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Presentations 18

  1. Spatiotemporal control of microglial absence is essential for the proper maturation of postmigratory neurons Invited International conference

    Yuki Hattori

    The 71th Annual Meeting Korean Association of Anatomists, Korea-China-Japan Webinar   2021.10.14 

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    Event date： 2021.10

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

  2. 胎生期大脳におけるミクログリア分布の時空間的制御とその生理学的意義

    服部祐季

    第44回日本神経科学大会/第1回 CJK 国際会議   2021.7.31 

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    Event date： 2021.7

    Language：English   Presentation type：Poster presentation  

  3. 胎生期大脳におけるミクログリア動態とニューロン産生への貢献 Invited

    服部祐季

    第126回日本解剖学会総会・全国学術集会  2021.3.29 

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    Event date： 2021.3

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

  4. 胎生期大脳におけるミクログリア分布の時空間的制御とその生理学的意義

    服部祐季

    第126回日本解剖学会総会・全国学術集会 日本解剖学会奨励賞受賞講演  2021.3.29 

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    Event date： 2021.3

  5. 胎生期大脳におけるミクログリア動態とニューロン産生への貢献

    服部祐季

    第14回神経発生討論会  2021.3.19 

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    Event date： 2021.3

    Language：Japanese  

  6. Microglial dynamics and its contribution to neurogenesis in mouse embryonic cerebral cortex

    Yuki Hattori

    2021.2.6 

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    Event date： 2021.2

    Language：English  

  7. Spatiotemporal control of microglial distribution in the developing cerebral cortex and its biological significance

    Yuki Hattori

    2020.9.19 

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    Event date： 2020.9

    Language：Japanese   Presentation type：Oral presentation (general)  

  8. Spatiotemporal control of microglial distribution in the developing cerebral cortex and its biological significance Invited

    Yuki Hattori

    2020.9.12 

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    Event date： 2020.9

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

  9. Transient absence of microglia underlies proper differentiation of the cortical plate

    Yuki Hattori

    German-Japanese Developmental Neuroscience Meeting 2020  2020.1.12 

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    Event date： 2020.1

    Language：English   Presentation type：Oral presentation (general)  

  10. Spatiotemporally controlled microglial absence is required for cortical neuron subtype specification

    Yuki Hattori, Yu Naito, Ayano Kawaguchi, Takaki Miyata

    2019.7 

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    Event date： 2019.7

    Language：English   Presentation type：Poster presentation  

  11. CXCL12-mediated zone-specific presence and absence of microglia fine-tune neurogenesis and neuronal subtype specification in embryonic cortex

    2018.2 

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    Event date： 2018.2

    Language：English   Presentation type：Poster presentation  

  12. 脳膜はマウス大脳原基におけるミクログリアの分布に関与する

    内藤裕, 服部祐季, 宮田卓樹

    第122回日本解剖学会総会・全国学術集会  2017.3.28 

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    Event date： 2017.3

    Language：Japanese   Presentation type：Oral presentation (general)  

  13. Spatiotemporally controlled microglial absence is required for cortical neuron subtype specification

    2018.9 

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    Language：English   Presentation type：Poster presentation  

  14. 胎生期大脳におけるCXCL12/CXCR4を介したミクログリアの局在変化は神経前駆細胞の分化状態とニューロンの個性化を調節する

    服部 祐季, 内藤 裕, 宮田 卓樹

    第41回日本神経科学大会  2018.7 

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    Language：Japanese   Presentation type：Poster presentation  

  15. 胎生期ミクログリアの時期依存的な分布変化・動態とその意義

    服部祐季

    第123回日本解剖学会総会・全国学術集会  2018.3.28 

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    Language：Japanese   Presentation type：Oral presentation (general)  

  16. 胎生中期皮質板からのミクログリアの一時的な抜け出しは、ニューロンの適切な個性獲得に必要である

    服部 祐季, 内藤 裕, 宮田 卓樹

    第124回日本解剖学会総会・全国学術集会  2019.3 

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    Language：Japanese   Presentation type：Oral presentation (general)  

  17. Spatiotemporally controlled microglial absence is required for cortical neuron subtype specification

    2019.3 

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    Language：English   Presentation type：Oral presentation (general)  

  18. Spatiotemporally controlled microglial absence is required for cortical neuron subtype specification

    2019.2 

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    Language：English   Presentation type：Poster presentation  

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KAKENHI (Grants-in-Aid for Scientific Research) 14

  1. 胎生期の脳発生過程におけるミクログリアの機能と母体炎症による影響の解明

    2016.4 - 2019.3

    科学研究費補助金 

    服部祐季

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    Authorship：Principal investigator 

  2. 胎生期の脳形成過程におけるミクログリアの動態と機能の解明

    2015.8 - 2017.3

    科学研究費補助金 

    服部祐季

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    Authorship：Principal investigator 

  3. 「脂質抗原」を標的とした新しいアレルギー応答の実証とその病態解明

    2012.4 - 2015.3

    科学研究費補助金 

    服部祐季

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    Authorship：Principal investigator 

  4. Microglial colonization into the brain and their heterogeneity in the embryonic brain

    Grant number：21H05624  2021.9 - 2023.3

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

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    Authorship：Principal investigator 

    Grant amount：\7800000 （ Direct Cost: \6000000 、 Indirect Cost：\1800000 ）

  5. ミクログリア多様性の理解と母体炎症による影響の解明

    2021.4 - 2028.3

    国立研究開発法人科学技術振興機構  創発的研究支援事業 

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    Authorship：Principal investigator  Grant type：Competitive

  6. ミクログリアのパトロール機構と神経系細胞との相互作用の時空間的解析

    Grant number：21K15330  2021.4 - 2024.3

    科学研究費助成事業  若手研究

    服部 祐季

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    Authorship：Principal investigator 

    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

    本研究では、マウス胎仔大脳におけるミクログリアのパトロール機構を制御する分子メカニズム、及び、周囲の神経系細胞との相互作用の理解を深める。まず、二光子顕微鏡を用いたin vivo観察系の改良を進め、細胞間ネットワークの時空間情報の実態把握とその評価法を整備し、細胞の運命を追跡できる解析基盤を確立する。そして、この観察・評価システムを利用して、ミクログリアの脳内パトロールの分子機構を明らかにし、ミクログリアと接触した神経前駆細胞のリアルタイムな動態把握と運命追跡を通じて、ミクログリアの脳発生過程における機能的役割の解明を目指す。

  7. 胎生期大脳におけるミクログリアのパトロール機構と脳発生への貢献

    2020.12 - 2022.3

    かなえ医薬振興財団  かなえ医薬振興財団研究助成金 

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    Authorship：Principal investigator 

  8. 母体慢性炎症がもたらす胎仔脳発生異常メカニズムの時空間的な統合理解

    2020.11 - 2021.12

    持田記念医学薬学振興財団  持田記念研究助成金 

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    Authorship：Principal investigator 

  9. 母体炎症による胎仔脳発生異常メカニズムの時空間的な統合理解

    2020.4 - 2021.3

    名古屋大学  名古屋大学基金 日比野基金 

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    Authorship：Principal investigator 

  10. ニューロンの適切な個性化とミクログリア分布の関連性

    2020.2 - 2021.3

    公益財団法人 上原記念生命科学財団  研究奨励金 

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    Authorship：Principal investigator 

  11. 母体炎症がもたらす胎児脳発生異常メカニズムの時空間的統合理解

    2020 - 2021

    公益信託 成茂基金  成茂神経科学研究助成金 

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    Authorship：Principal investigator 

  12. Spatiotemporal control of microglial distribution in the developing cerebral cortex and its biological significance

    Grant number：18K15003  2018.4 - 2021.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    Hattori Yuki

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    Authorship：Principal investigator 

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

    Microglia change their distribution in a stage-dependent manner in the embryonic cerebral cortex. In mice, intrapallial microglial distribution is initially homogenous until embryonic day (E) 14, but these cells temporarily disappear from the cortical plate (CP) from E15 to E16. However, the mechanism and significance of this absence are unknown. We demonstrated that microglia bidirectionally migrate via attraction by CXCL12 released from the meninges and SVZ, and thereby exit the midembryonic CP. In addition, postmigratory neurons exposed to excessive microglia showed the disturbed expression pattern of 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.

  13. 胎生期の脳発生過程におけるミクログリアの機能と母体炎症による影響の解明

    Grant number：16J06207  2016.4 - 2019.3

    日本学術振興会  科学研究費助成事業 特別研究員奨励費  特別研究員奨励費

    服部 祐季

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    本年度は、マウス胎生中期におけるミクログリアの動態および機能について研究を進め、論文を2報発表した。1報目は、ミクログリアが神経前駆細胞の分化を促進し、Tbr2陽性の中間前駆細胞の数を増すということ、またそういった機能を十分に発揮するには、ミクログリアがCXCL12/CXCR4システム（CXCL12は脳室下帯に存在する中間前駆細胞が発現し、CXCR4はミクログリアが発現する）を介して脳壁内を広く移動することが重要であることを明らかにし、Genes to Cells誌に発表した。
    続いて2報目では、脳発生・神経発生学の研究に汎用される子宮内電気穿孔法（in utero electroporation, IUE）の「プラスミドDNAを脳室に注入する」というステップによって、通常では脳壁全体に散らばって存在するミクログリアが脳室面近くに並ぶように集積すること、そしてこの変化は、ミクログリアが発現するToll様受容体9（Toll-like receptor 9, TLR9）のDNA認識によって引き起こされることを明らかにした。また、TLR9のアンタゴニストであるODN 2088をプラスミドDNAと同時に脳室内に注入することによって、ミクログリアの異常な集積が緩和されることを見出した。この成果はeNeuro誌に発表し、また同誌のコミュニティサイトのeNeuro blogにおいてEditor’s picksとして取り上げられた。
    一方で、本課題開始時より取り組んでいるミクログリアの時期依存的な分布変化のメカニズムとその意義に関して論文をまとめ、投稿した。現在、in revisionの段階であり、追加実験を進めている。

  14. 胎生期の脳形成過程におけるミクログリアの動態と機能の解明

    Grant number：15H06277  2015.8 - 2017.3

    日本学術振興会  科学研究費助成事業 研究活動スタート支援  研究活動スタート支援

    服部 祐季

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    本研究は、胎生期大脳におけるミクログリアの存在意義および神経系細胞産生への貢献について明らかにすることを目的とする。平成27年度は、以下の項目について成果を得た。
    (1)マウス大脳におけるミクログリアの分布と胎齢進行に伴う分布・動態変化を、切片免疫染色および脳原基スライス培養下でのライブ観察にて網羅的に調べたところ、胎生前期までは脳実質全体に散在するのに対し、胎生中期以降は神経系細胞の産生の場である脳室帯（VZ）／脳室下帯（SVZ）に集積する様子を捉えた。そこで、VZ/SVZに存在する神経系中間前駆細胞が発現する分子群に着目し、それらに対する阻害剤を用いた機能検証を進め、ミクログリアの移動・分布の規定に重要な分子を同定した。
    (2)ミクログリアが神経前駆細胞の産生・運命決定に寄与する可能性について検証した。in vivoでのToll様受容体（TLR）リガンド・薬剤投与によるミクログリアの活性化・除去による検討、セルソーターで回収したミクログリアと脳原基細胞の共培養実験から、ミクログリアがTbr2陽性の神経系中間前駆細胞の数を増す可能性が示された。
    (3)脳原基の細胞動態観察に頻用されるスライス培養ではin vivo環境を一定時間は維持するが、長時間に及ぶ観察では血管構造が破綻する等の問題が生じる。そこで、脳に損傷を与えることなく、より生理的な条件下で三次元モニタリングを可能にする「二光子顕微鏡を用いた胎仔脳内in vivoライブ観察法」の確立を目指し、試行を進めた。母体の拍動や羊水中の胎仔の動きに由来する揺動を抑えることのできる観察条件を整え、これまでに子宮越しでのミクログリアの継続したタイムラプス観察が約半日まで達成できている。
    得られた成果は、第9回神経発生討論会（ポスター）、第121回日本解剖学会総会全国学術集会（口演）で発表した。

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To the head of KAKENHI (Grants-in-Aid for Scientific Research).▲
 

Teaching Experience (On-campus) 4

  1. 肉眼解剖学

    2022

  2. 発生学

    2022

  3. 肉眼解剖学

    2021

  4. 発生学

    2021

To the head of Teaching Experience (On-campus).▲