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Study of the program underlying the mammalian complex brain formation

Research Project

Project/Area Number 18H04003
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Matsuzaki Fumio  国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (10173824)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥43,940,000 (Direct Cost: ¥33,800,000、Indirect Cost: ¥10,140,000)
Fiscal Year 2021: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2020: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2019: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2018: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Keywords神経幹細胞 / 脳発生 / 複雑脳 / フェレット / 大脳皮質 / マイクロカラム / 神経前駆細胞 / 脳進化 / 哺乳類 / 細胞系譜 / 単一細胞解析 / 神経発生 / 脳幹細胞 / クローンサイズ / 多様性 / 脳回 / 高次能 / 幹細胞 / フェッレット / 発生 / 動態 / 不均一性
Outline of Final Research Achievements

During ferret cortical development, neural stem cell called apical radial glia (aRG) frequently generate sibling cells, which express Hes1 and bear a short basal process. These cell, termed short radial glia (sRG)l undergo a couple of apical cell divisions with nuclear interkinetic migration just like aRG. Interestingly, the appearance of sRG is stochastic in the lineages. These cells differentiate intermediate progenitor cells expressing Ascl1, and continue several rounds of divisions to produce neurons. While we examine these cell division patterns by time-lapse imaging of slice culture, the consecutive cell cycle number is limited. To overcome this limit, we started in vivo cell lineage analysis using "barclock", which is genome-inserted barcode that accumulates mutation in the presense of genome-editor, hybrid of dCas9 with Cytosine deaminase.

Academic Significance and Societal Importance of the Research Achievements

脳の発生は神経管の形成に始まり、まず幹細胞となる神経上皮細胞の増殖、ついで非対称分裂による分化細胞の形成へと進む。哺乳類の進化過程で、脳のサイズや複雑さは著しく増加するが、それは神経上皮細胞の増殖の亢進だけではなく、神経発生期にも増殖脳、言い換えると未分化性が保たれる。この傾向は霊長類でよく知られているが、我々のフェレットをモデルにした解析から食肉類のにも共通に存在することが明らかとなった。さらに幅広い系統の分析が必要であるが、これが哺乳類の脳の拡張と複雑化の一般的なメカニズムであることが示唆される重要な発見であり、脳の複雑化に発生、構造的な共通性の探索という新しい学問の展開の出発点になる。

Report

(5 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (25 results)

All 2022 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (12 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 12 results,  Open Access: 12 results) Presentation (12 results) (of which Int'l Joint Research: 6 results,  Invited: 6 results)

  • [Int'l Joint Research] British Columbia大学(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] The cardiopharyngeal mesoderm contributes to lymphatic vessel development in mouse2022

    • Author(s)
      Maruyama Kazuaki、Miyagawa-Tomita Sachiko、Haneda Yuka、Kida Mayuko、Matsuzaki Fumio、Imanaka-Yoshida Kyoko、Kurihara Hiroki
    • Journal Title

      eLife

      Volume: 11 Pages: 1-19

    • DOI

      10.7554/elife.81515

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selective translation of epigenetic modifiers affects the temporal pattern and differentiation of neural stem cells2022

    • Author(s)
      Wu Quan、Shichino Yuichi、Abe Takaya、Suetsugu Taeko、Omori Ayaka、Kiyonari Hiroshi、Iwasaki Shintaro、Matsuzaki Fumio
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 470-470

    • DOI

      10.1038/s41467-022-28097-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Amyloidogenic processing of amyloid β protein precursor (APP) is enhanced in the brains of alcadein α-deficient mice2020

    • Author(s)
      Gotoh N、Saito Yi、Hata S、Saito H、Ojima D、Murayama Ci、Shigeta M、Abe T、Konno D、Matsuzaki F、Suzuki T、Yamamoto T
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 28 Pages: 9650-9662

    • DOI

      10.1074/jbc.ra119.012386

    • NAID

      120007116485

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative Analysis of Brain Stiffness Among Amniotes Using Glyoxal Fixation and Atomic Force Microscopy2020

    • Author(s)
      Iwashita Misato、Nomura Tadashi、Suetsugu Taeko、Matsuzaki Fumio、Kojima Satoshi、Kosodo Yoichi
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8 Pages: 1-15

    • DOI

      10.3389/fcell.2020.574619

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mechanical forces drive ordered patterning of hair cells in the mammalian inner ear2020

    • Author(s)
      Cohen Roie、Amir-Zilberstein Liat、Hersch Micha、Woland Shiran、Loza Olga、Taiber Shahar、Matsuzaki Fumio、Bergmann Sven、Avraham Karen B.、Sprinzak David
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 1-12

    • DOI

      10.1038/s41467-020-18894-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Blood and lymphatic systems are segregated by the FLCN tumor suppressor2020

    • Author(s)
      Tai-Nagara I, Hasumi Y, Kusumoto D, Hasumi H, Okabe K, Ando T, Matsuzaki F, Itoh F, Saya H, Liu C, Li W, Mukouyama Y, Linehan WM, Liu X, Hirashima M, Suzuki Y, Funasaki S, Satou Y, Furuya M, Baba M, Kubota Y.
    • Journal Title

      Nat. Commun.

      Volume: 11 Issue: 1 Pages: 6314-6314

    • DOI

      10.1038/s41467-020-20156-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Notch1 and Notch2 collaboratively maintain radial glial cells in mouse neurogenesis2020

    • Author(s)
      Mase Shun、Shitamukai Atsunori、Wu Quan、Morimoto Mitsuru、Gridley Thomas、Matsuzaki Fumio
    • Journal Title

      Neuroscience Research

      Volume: Available online 11 December Pages: 1-11

    • DOI

      10.1016/j.neures.2020.11.007

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endfoot regeneration restricts radial glial state and prevents translocation into the outer subventricular zone in early mammalian brain development2019

    • Author(s)
      Fujita Ikumi、Shitamukai Atsunori、Kusumoto Fumiya、Mase Shun、Suetsugu Taeko、Omori Ayaka、Kato Kagayaki、Abe Takaya、Shioi Go、Konno Daijiro、Matsuzaki Fumio
    • Journal Title

      Nature Cell Biology

      Volume: 22 Issue: 1 Pages: 26-37

    • DOI

      10.1038/s41556-019-0436-9

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dmrt factors determine the positional information of cerebral cortical progenitors via differential suppression of homeobox genes.2019

    • Author(s)
      Konno D, Kishida C, Maehara K, Ohkawa Y, Kiyonari H, Okada S, Matsuzaki F
    • Journal Title

      Development

      Volume: 146 Issue: 15 Pages: 174243-174243

    • DOI

      10.1242/dev.174243

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reconstruction of Par-dependent polarity in apolar cells reveals a dynamic process of cortical polarization2019

    • Author(s)
      Kono K, Yoshiura S, Fujita I, Okada Y, Shitamukai A, Shibata T, Matsuzaki F
    • Journal Title

      eLife

      Volume: 8 Pages: 1-31

    • DOI

      10.7554/elife.45559

    • NAID

      120006653006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isl1-expressing non-venous cell lineage contributes to cardiac lymphatic vessel development.2019

    • Author(s)
      Maruyama K, Miyagawa-Tomita S, Mizukami K, Matsuzaki F, Kurihara H.
    • Journal Title

      Dev Biol

      Volume: 452 Issue: 2 Pages: 134-143

    • DOI

      10.1016/j.ydbio.2019.05.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lzts1 controls both neuronal delamination and outer radial glial-like cell generation during mammalian cerebral development2019

    • Author(s)
      Kawaue T.、Shitamukai A.、Nagasaka A.、Tsunekawa Y.、Shinoda T.、Saito K.、Terada R.、Bilgic M.、Miyata T.、Matsuzaki F.、Kawaguchi A.
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 2780-2780

    • DOI

      10.1038/s41467-019-10730-y

    • NAID

      120006649601

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Exploring the relationship of progenitor subtypes in and between gyrencephalic species at the single cell level” speaker Symposium.2022

    • Author(s)
      Fumio Matsuzaki
    • Organizer
      Neuro2022
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Exploring the relationship of progenitor subtypes in and between gyrencephalic species2022

    • Author(s)
      Fumio Matsuzaki
    • Organizer
      24nd biannual Conference of International Society of Developmental Neuroscience
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regeneration ability of the epithelial structure in neural stem cells during mammalian brain development.2020

    • Author(s)
      Ikumi Fujita, Atsunori Shitamukai, Fumiya Kusumoto, Shun Mase, Taeko Suetsugu, Ayaka Omori, Kagayaki Kato, Takaya Abe, Go Shioi, Daijiro Konno, Fumio Matsuzaki
    • Organizer
      第72回日本細胞生物学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Regeneration of the epithelial structure in neural stem cells during mammalian brain development.2020

    • Author(s)
      Ikumi Fujita, Atsunori Shitamukai, Fumiya Kusumoto, Shun Mase, Taeko Suetsugu, Ayaka Omori, Kagayaki Kato, Takaya Abe, Go Shioi, Daijiro Konno, Fumio Matsuzaki
    • Organizer
      Cell Bio Virtual 2020 Meeting (The American Society for Cell Biology)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regeneration ability of the epithelial structure in neural stem cells during mammalian brain development.2020

    • Author(s)
      Ikumi Fujita, Atsunori Shitamukai, Fumiya Kusumoto, Shun Mase, Taeko Suetsugu, Ayaka Omori, Kagayaki Kato, Takaya Abe, Go Shioi, Daijiro Konno, Fumio Matsuzaki
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The radial fiber-mediated FGF signal ensures the feedback signaling system from neurons to radial glial cells in the developing cerebral cortex.2020

    • Author(s)
      Atsunori Shitamukai,Fumio Matsuzaki
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Structural plasticity of neural stem cells in mammalian brain development2019

    • Author(s)
      Fumio Matsuzaki
    • Organizer
      Baikal Neuroscience Meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Structural plasticity of neural stem cells in mammalian brain development.2019

    • Author(s)
      Fumio Matsuzaki
    • Organizer
      The 10th IBRO World Congress of Neuroscience IBRO 2019
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] How has the brain expanded and acquired complexity in the mammalian evolution?2019

    • Author(s)
      Fumio Matsuzaki
    • Organizer
      第42回分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Structural plasticity of neural stem cells in mammalian brain development.2019

    • Author(s)
      Fumio Matsuzaki
    • Organizer
      Baikal Neuroscience Meeting 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] How has the brain expanded and acquired complexity in the mammalian2019

    • Author(s)
      Fumio Matsuzaki,Yuji Tsunekawa, Taeko Suetsugu, Ikumi Fujita, Quan Wu, Atsunori Shitamukai, Ayaka Omori, Osamu Nishimura, Shigehiro Kuraku
    • Organizer
      第42回分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 非分裂細胞に対するノックイン技術HITIとその展望2019

    • Author(s)
      恒川雄二
    • Organizer
      ウイルスベクター開発研究センターキックオフシンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited

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Published: 2018-04-23   Modified: 2024-01-30  

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