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"Interplay of intercellular communication in regulating developmental time

Planned Research

Project AreaInterplay of developmental clock and extracellular environment in brain formation
Project/Area Number 16H06483
Research Category

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

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionWaseda University

Principal Investigator

Hanashima Carina  早稲田大学, 教育・総合科学学術院, 教授 (80469915)

Co-Investigator(Kenkyū-buntansha) 高里 実  国立研究開発法人理化学研究所, 多細胞システム形成研究センター, チームリーダー (40788676)
Project Period (FY) 2016-06-30 – 2021-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥109,330,000 (Direct Cost: ¥84,100,000、Indirect Cost: ¥25,230,000)
Fiscal Year 2020: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2019: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2018: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2017: ¥24,310,000 (Direct Cost: ¥18,700,000、Indirect Cost: ¥5,610,000)
Fiscal Year 2016: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000)
Keywords大脳新皮質 / 神経幹細胞 / 発生時計 / 層ニューロン / 転写制御ネットワーク / 大脳皮質 / 幹細胞 / 細胞間情報伝達 / 転写制御 / 発生時間 / 細胞間相互作用 / 時間制御 / 分化 / 発生・分化 / 脳・神経 / 神経科学 / シグナル伝達 / 細胞・組織
Outline of Final Research Achievements

In this study, we aimed to elucidate the regulatory mechanisms of the developmental clock in brain formation, focusing on the temporal production of neurons in the cerebral cortex and the molecular identity of feedback signal-mediated neuronal production transition. During the production period of deep- and upper-layer neurons, we manipulated gene expression in cortical progenitor cells and revealed that the intracellular localization of transcription factor determines the temporal competence of progenitor cells and the timing of upper-layer neuron production. Furthermore, we analyzed the extrinsic mechanisms that determine the differentiation and positioning of layer subtype neurons in the cerebral cortex, and revealed the interaction between the intrinsic transcriptional regulatory network and extracellular signaling in the spatiotemporal control of brain formation.

Academic Significance and Societal Importance of the Research Achievements

細胞間の相互作用を介したシグナルが、神経幹細胞の発生時計を制御するという仮説が40年前に提唱されたが、その分子実体については不明な点が多く残されていた。本研究では、ニューロンと神経幹細胞の細胞間シグナリングに焦点を当て、細胞内の転写因子局在と時間的に変化する場からのフィードバックシグナルが発生時計を制御するという新たな知見を得た。このシステムの破綻は神経疾患の発症につながると考えられる一方で、ヒトとマウスなどの胎生期間や細胞周期等の発生時間のパラメータが大きく異なる種間のニューロン産生の相対的な調節にもつながり、脳神経回路の構築原理を明らかにする上で重要であると考えられる。

Report

(6 results)
  • 2022 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (60 results)

All 2023 2022 2021 2020 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (45 results) (of which Int'l Joint Research: 16 results,  Invited: 10 results) Remarks (4 results)

  • [Int'l Joint Research] University of Freiburg(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Involvement of strawberry notch homologue 1 in neurite outgrowth of cortical neurons2022

    • Author(s)
      Erkhembaatar Munkhsoyol、Yamamoto Iroha、Inoguchi Fuduki、Taki Kosuke、Yamagishi Satoru、Delaney Leanne、Mariko Nishibe、Abe Takaya、Kiyonari Hiroshi、Hanashima Carina、Naka‐kaneda Hayato、Ihara Dai、Katsuyama Yu
    • Journal Title

      Development, Growth & Differentiation

      Volume: 64 Issue: 7 Pages: 379-394

    • DOI

      10.1111/dgd.12802

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Beyond Axon Guidance: Roles of Slit-Robo Signaling in Neocortical Formation2020

    • Author(s)
      Gonda Y, Namba T, Hanashima C.
    • Journal Title

      Front Cell Dev Biol

      Volume: 8 Pages: 607415-607415

    • DOI

      10.3389/fcell.2020.607415

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transcription and Beyond: Delineating FOXG1 Function in Cortical Development and Disorders2020

    • Author(s)
      Hou Pei-Shan、hAilin Darren O、Vogel Tanja、Hanashima Carina
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 14 Pages: 1-14

    • DOI

      10.3389/fncel.2020.00035

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sensory cortex wiring requires preselection of short- and long-range projection neurons through an Egr-Foxg1-COUP-TFI network2019

    • Author(s)
      Hou Pei-Shan、Miyoshi Goichi、Hanashima Carina
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1-18

    • DOI

      10.1038/s41467-019-11043-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RECK in Neural Precursor Cells Plays a Critical Role in Mouse Forebrain Angiogenesis2019

    • Author(s)
      Li Huiping、Miki Takao、Almeida Glicia Maria de、Hanashima Carina、Matsuzaki Tomoko、Kuo Calvin J.、Watanabe Naoki、Noda Makoto
    • Journal Title

      iScience

      Volume: 19 Pages: 559-571

    • DOI

      10.1016/j.isci.2019.08.009

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diencephalic progenitors contribute to the posterior septum through rostral migration along the hippocampal axonal pathway2018

    • Author(s)
      Watanabe Keisuke、Irie Koichiro、Hanashima Carina、Takebayashi Hirohide、Sato Noboru
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 1-13

    • DOI

      10.1038/s41598-018-30020-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evolutionary conservation and conversion of Foxg1 function in brain development2017

    • Author(s)
      Kumamoto Takuma、Hanashima Carina
    • Journal Title

      Development, Growth & Differentiation

      Volume: 59 Issue: 4 Pages: 258-269

    • DOI

      10.1111/dgd.12367

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Sensitive and Versatile In Situ Hybridization Protocol for Gene Expression Analysis in Developing Amniote Brains2017

    • Author(s)
      Hou Pei-Shan、Kumamoto Takuma、Hanashima Carina
    • Journal Title

      Methods Mol Biol

      Volume: 1650 Pages: 319-334

    • DOI

      10.1007/978-1-4939-7216-6_22

    • ISBN
      9781493972159, 9781493972166
    • Related Report
      2017 Annual Research Report
  • [Journal Article] A Sensitive and Versatile In Situ Hybridization Protocol for Gene Expression Analysis in Developing Amniote Brains2017

    • Author(s)
      Hou Pei-Shan、Kumamoto Takuma、Hanashima Carina
    • Journal Title

      Methods in Molecular Biology

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 大脳皮質層ニューロンの分化と統合メカニズム2016

    • Author(s)
      當麻憲一, 花嶋かりな
    • Journal Title

      生体の科学

      Volume: 68 Pages: 19-23

    • Related Report
      2016 Annual Research Report
  • [Presentation] Molecular control of neuronal subtype specification and integration in the cerebral cortex2023

    • Author(s)
      Carina Hanashima
    • Organizer
      International Symposium on Neural Development and Diseases
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neuronal subtype transitions and integration in the cerebral cortex2022

    • Author(s)
      Carina Hanashima
    • Organizer
      Gordon Research Conference ‘Molecular and Cellular Neurobiology’
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Specification and integration of glutamatergic neuron subtypes in the cerebral cortex2022

    • Author(s)
      Carina Hanashima
    • Organizer
      ISN-APSN 2022, Symposium ‘Cerebral Cortex Assembly: neuron migration, folding and connectivity’
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Foxg1 and Brn2 cooperatively regulate the temporal production of upper-layer neurons in the developing neocortex2022

    • Author(s)
      Zi Chao Ngiam, Kenichi Toma, and Carina Hanashima
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Mechanisms of spiny stellate-specific dendritic morphology acquisition in the neocortex2022

    • Author(s)
      Misa Cho and Carina Hanashima
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Foxg1 gene in whisker pattern formation in the developing sensory system2022

    • Author(s)
      Mai Onuki and Carina Hanashima
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The mechanisms of sensory input neuron production in the avian pallium2022

    • Author(s)
      Ryoka Katayama, Takuma Kumamoto, Chiaki Ohtaka-Maruyama, and Carina Hanashima
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Spatiotemporal dynamics of neocortical layer 4 development2022

    • Author(s)
      Naoto Ohte and Carina Hanashima
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Transcriptional and post-transcriptional mechanisms of Brn2-mediated upper-layer neurogenesis in the cerebral cortex2022

    • Author(s)
      Zi Chao Ngiam and Carina Hanashima
    • Organizer
      第45回日本神経科学大会/第65回日本神経化学会大会/第32回日本神経回路学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Retrosplenial cortexの特異性に関わる遺伝子と層構造構築過程の解析2022

    • Author(s)
      白坂みさの、花嶋かりな
    • Organizer
      第45回日本神経科学大会/第65回日本神経化学会大会/第32回日本神経回路学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 大脳新皮質第 4 層発達過程の時空間的遺伝子発現と統合ダイナミクス2022

    • Author(s)
      大手直人、侯 珮珊、西山千尋、花嶋かりな
    • Organizer
      第45回日本神経科学大会/第65回日本神経化学会大会/第32回日本神経回路学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Robo1 signaling-mediated Golgi apparatus dynamics determine the dendritic morphology of layers 2/3 pyramidal neurons in the cerebral cortex2022

    • Author(s)
      Yuko Gonda and Carina Hanashima
    • Organizer
      第45回日本神経科学大会/第65回日本神経化学会大会/第32回日本神経回路学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Mechanisms of neuronal subtype transition and integration in the cerebral cortex2022

    • Author(s)
      Carina Hanashima
    • Organizer
      The International Symposium on Development and Plasticity of Neural Systems
    • Related Report
      2020 Annual Research Report
  • [Presentation] Spatiotemporal dynamics of neocortical layer 4 neuron development during the postnatal period2021

    • Author(s)
      Naoto Ohte, Hou Pei-Shan, Chihiro Nishiyama, and Carina Hanashima
    • Organizer
      第44回日本神経科学大会/第1回CJK国際会議
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of the specific genes and laminae constructions of retrosplenial cortex2021

    • Author(s)
      Misano Shirasaka, Marina Fujimoto, and Carina Hanashima
    • Organizer
      第44回日本神経科学大会/第1回CJK国際会議
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular control of layer-specific dendritic formation of neocortical neurons2021

    • Author(s)
      Yuko Gonda, Tatsunori Seki, and Carina Hanashima
    • Organizer
      第44回日本神経科学大会/第1回CJK国際会議
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of early-born neurons in the assembly of the neocortical circuit2020

    • Author(s)
      Carina Hanashima
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Cellular and molecular mechanisms of neocortical integration through area-specific migration mode2020

    • Author(s)
      Rui Iizuka, Peishan Hou, Chihiro Nishiyama, and Carina Hanashima
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Spatiotemporal dynamics of molecular and laminar organization of the retrosplenial cortex2020

    • Author(s)
      Misano Shirasaka, Marina Fujimoto, and Carina Hanashima
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Transcription regulation of neurite growth by Strawberry Notch Homolog 12020

    • Author(s)
      Munkhsoyol Erkhembaatar, Keito Minemori, Iroha Yamamoto, Takashi Imaz, Fuduki Inoguchi, Carina Hanashima, Satoru Yamagishi, Hayato Naka-Kaneda, and Yu Katsuyama
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 脳梁膨大後部皮質特有の神経回路構築を担う分子機構の解析2019

    • Author(s)
      白坂みさの, 藤本真里奈, 花嶋かりな
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 細胞間相互作用を介した大脳皮質領野形成機構の解析2019

    • Author(s)
      飯塚 瑠伊, 侯 珮珊、西山 千尋, 花嶋 かりな
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 大脳皮質領野形成における放射状グリア細胞の役割2019

    • Author(s)
      入江 浩一郎, 西山 千尋, 花嶋 かりな
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 細胞間相互作用を介した大脳皮質領野形成機構の解析2019

    • Author(s)
      飯塚 瑠伊, 侯 珮珊、西山 千尋, 花嶋 かりな
    • Organizer
      第42回日本神経科学大会 Neuro2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] 大脳皮質領野形成における放射状グリア細胞の役割2019

    • Author(s)
      入江 浩一郎, 西山 千尋, 花嶋 かりな
    • Organizer
      第42回日本神経科学大会 Neuro2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] Mechanisms of neuronal subtype specification and integration in the cerebral cortex2019

    • Author(s)
      Carina Hanashima
    • Organizer
      IBRO 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanisms of neuronal subtype specification and integration in the cerebral cortex2019

    • Author(s)
      Carina Hanashima
    • Organizer
      Baikal Neuroscience Meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Preselection of long- and short-range projection neurons through reciprocal Foxg1 and COUP-TFI actions establish the sensory cortical circuit2019

    • Author(s)
      侯 珮珊, 花嶋 かりな
    • Organizer
      52nd Annual Meeting of JSDB
    • Related Report
      2019 Annual Research Report
  • [Presentation] Neuronal subtype transitions and integration in the cerebral cortex.2018

    • Author(s)
      Hanashima, C.
    • Organizer
      Gordon Research Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Transcriptional control of fate specification and circuit specialization in the neocortex.2018

    • Author(s)
      Hanashima, C.
    • Organizer
      The 41st Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Peishan Hou, Carina Hanashima2018

    • Author(s)
      Transcriptional mechanisms underlying the establishment of sensory areas
    • Organizer
      The 41st Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2018 Annual Research Report
  • [Presentation] Roles of radial glia in the assembly of cortical areas2018

    • Author(s)
      Irie, K., Nishiyama, C., Hanashima, C.
    • Organizer
      MBSJ 2018 第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Retrosplenial cortex の層構造とニューロンサブタイプについての解析2018

    • Author(s)
      藤本 真里奈 , 小田 地人 , 花嶋 かりな
    • Organizer
      MBSJ 2018 第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mechanisms that establish boundary between motor and somatosensory areas of the neocortex2018

    • Author(s)
      Iizuka, R., Hou, P.S., Nishiyama, C., Hanashima, C.
    • Organizer
      MBSJ 2018 第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Regulation of apical dendritic patterning of neocortical pyramidal neurons2018

    • Author(s)
      Gonda, Y., Seki, T., Hanashima, C.
    • Organizer
      ISDN 2018 The 22nd Biennial International Society for Developmental Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transcriptional mechanisms underlying the establishment of sensory areas2018

    • Author(s)
      Hou, P.S., Hanashima, C.
    • Organizer
      ISDN 2018 The 22nd Biennial International Society for Developmental Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 時空間制御による大脳皮質ニューロン産生のメカニズム2018

    • Author(s)
      花嶋かりな
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] The Role of Foxg1 in the Development of Neocortex2017

    • Author(s)
      Hanashima, C.
    • Organizer
      International Symposium and Conference on Congenital Anomaly and Developmental Biology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanisms of neuronal subtype transitions and integration in the cerebral cortex2017

    • Author(s)
      Hanashima, C.
    • Organizer
      Janelia Conference 2017 ‘Control of Neuronal Identity II’
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Transcriptional mechanisms underlying the establishment of sensory areas2017

    • Author(s)
      Hou, P.S., Hanashima, C.
    • Organizer
      次世代脳プロジェクト
    • Related Report
      2017 Annual Research Report
  • [Presentation] Mechanisms that balance neuronal subtype production in the developing neocortex2017

    • Author(s)
      Toma, K. Hanashima, C.
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Mechanisms that balance neuronal subtype production in the developing neocortex2016

    • Author(s)
      Toma, K. Hanashima, C.
    • Organizer
      Neuroscience 2016, SfN’s 46th Annual Meeting
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Temporal dynamics of laminar subtype neuron differentiation in developing mouse neocortex2016

    • Author(s)
      Hou, P.S. Hanashima, C.
    • Organizer
      Neuroscience 2016, SfN’s 46th Annual Meeting
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Establishing neuronal identity in the cerebral cortex2016

    • Author(s)
      Hanashima, C.
    • Organizer
      Volga Neuroscience Meeting 2016 ‘Molecular Neuroscience’
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanisms that establish cell fate in the cerebral cortex2016

    • Author(s)
      Hanashima, C.
    • Organizer
      第39回日本分子生物学会
    • Related Report
      2016 Annual Research Report
  • [Remarks] https://hanashima-lab.wixsite.com/waseda

    • Related Report
      2020 Annual Research Report
  • [Remarks] Hanashima Lab homepage

    • URL

      https://hanashima-lab.wixsite.com/waseda

    • Related Report
      2019 Annual Research Report
  • [Remarks] 研究室HP

    • URL

      https://hanashima-lab.wixsite.com/waseda

    • Related Report
      2018 Annual Research Report 2016 Annual Research Report
  • [Remarks] 花嶋研究室HP

    • URL

      https://hanashima-lab.wixsite.com/waseda

    • Related Report
      2017 Annual Research Report

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Published: 2016-07-04   Modified: 2024-01-30  

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