Unexpectedly wide-range cell-cell contact via Delta-presenting lamellipodia-like protrusions in the mouse neuroepithelium
| Project/Area Number |
18K14837
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 46020:Anatomy and histopathology of nervous system-related
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| Research Institution | Kyoto University (2021-2022)
Nagoya University (2018-2019) |
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Principal Investigator |
Kawaue Takumi 京都大学, 高等研究院, 特定助教 (50793858)
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| Project Period (FY) |
2021-03-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 発生・分化 / 細胞間相互作用 / 神経前駆細胞 / Delta-Notchシグナル伝達 / 細胞運命選択 / 細胞間接触 / Delta-Notchシグナル / 神経上皮 |
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| Outline of Research at the Start |
胎生期の大脳原基において、神経前駆細胞は周囲の分化細胞との接触を介したDelta-Notchシグナル伝達を利用して、「分化」か「未分化」の運命選択を行う。従来、そのシグナル伝達は直近の隣接細胞間のみで行われる狭い範囲のものを想定してきたが、申請者は最近、2~4細胞先の遠方の細胞にまで接触する葉状仮足を新規に発見したことで、そのやり取りはより広範囲に渡る可能性（仮説）があると考えた。本研究では、1）葉状仮足の消失実験を通してこの仮説を検証するとともに、2）Delta-Notchシグナル伝達が活性化されるための「細胞間接触（部位・面積・時間）」とはいかなるものか、その本質を問う。
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| Outline of Final Research Achievements |
During mammalian brain development, cell contact-mediated interactions, such as Delta-Notch signaling, are important for the cell fate choice of the newborn cells. Although the fundamental molecular mechanism of Delta-Notch signaling is well known, how Delta-presenting cells contact with the neighbors to induce their Notch activation in developing 3D tissues has been challenging to address. In this study, we demonstrated that membrane-bound Delta molecules were enriched in lamellipodia-like protrusions that were extended from the apical process of differentiating cells. In addition, the decrease in lamellipodia-like structures increased the number of differentiating cells in the cerebral cortex. These results suggest that cell-cell contacts through microstructures are involved in cell fate choice for newborn cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、哺乳類の大脳が形成される過程における細胞の運命選択の仕組みについて理解が深まった。また、細胞が持つ微細構造とそのダイナミクスが、細胞間のシグナル伝達の範囲を規定する重要な要素であることが明らかとなった。発展的展望として、シグナル伝達が活性化されるために必要な実質的な細胞間接触（接触面積・時間）について理解する必要があり、これから得られる知見は細胞の運命選択のみならず発生（正常・がん）・再生・疾患のメカニズム解明の糸口となる期待がある。
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Report
(4 results)
Research Products
(8 results)
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[Journal Article] Elasticity-based boosting of neuroepithelial nukleokinesis via indirect energy transfer from mother to daughter2018
Author(s)
Tomoyasu Shinoda, Arata Nagasaka, Yasuhiro Inoue, Ryo Higuchi, Yoshiaki Minami, Kagayaki Kato, Makoto Suzuki, Takefumi Kondo, Takumi Kawaue, Kanako Saito, Naoto Ueno, Yugo Fukazaawa, Masaharu Nagayama, Takashi Miura, Taiji Adachi, Takaki Miyata
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Journal Title
PLoS Biology
Volume: 16
Issue: 4
Pages: 2004426-2004426
DOI
Related Report
Peer Reviewed / Open Access
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