A possible mechanism for enlargement of the cortex in placental mammals by the cellular mRNA transport system
| Project/Area Number |
20K07237
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 48010:Anatomy-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
若松 義雄 東北大学, 医学系研究科, 准教授 (60311560)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 放射状グリア細胞 / 細胞周期因子 / mRNA / 進化 / 大脳皮質 / mRNA輸送 |
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| Outline of Research at the Start |
大脳皮質の形成過程では、神経幹細胞として働く放射状グリア（RG）細胞が適切に増殖・分化し、多様なニューロンが産生される。細胞周期因子CyclinD2のmRNAはRG細胞の基底膜側突起の末端部まで輸送され、CyclinD2の3’UTR領域に輸送に必要な配列が存在する。この輸送配列は哺乳類の中でも有胎盤類にのみ保存されており、突起に輸送されるCyclinD2 が、有胎盤類の進化過程における大脳皮質の発達に貢献する可能性が考えられる。そこで本研究では、有胎盤類、有袋類および鳥類胚を用いて大脳皮質形成におけるCyclinD2 mRNAの輸送の役割を解析する。
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| Outline of Final Research Achievements |
The vertebrate brain is formed by the proliferation and differentiation of radial glial (RG) cells. mRNAs of CyclinD2, a cell cycle regulator, are transported to the basal end-foot of the RG cell dependent on its 3´UTR “zip code” (cis-acting transport element, CTE). We found a basal-to-apical translocation of CyclinD2 proteins along the basal processes, indicating that CyclinD2 proteins in the basal end-feet will be transported to the nuclei to modulate the cell cycle progression. In CTE deleted mice, CyclinD2 mRNA no longer localized in the basal end-feet, and the cortical thickness was reduced. Interestingly, the CTE is only conserved in placental mammals among various vertebrates. Consistently, CyclinD2 mRNAs were not detected in the basal end-feet of the opossum, a marsupial mammal, nor in chick. The basal transport of CyclinD2 mRNA in the RG cells might be involved in forming a larger cortex of placental mammals.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、ヒトを含む有胎盤類の進化過程において、大脳皮質の拡大がどのようなメカニズムで起きたのかという未知の問いへアプローチすることを目的としている。本研究によって、独自に見出した神経幹細胞内CyclinD2 mRNA輸送の新たな生物学的意義を明らかにし、このユニークな機構が有胎盤類のみに存在することを発見した。本研究は、有胎盤類の脳進化メカニズムの一端を明らかにできた点で学術的意義がある。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Paternal age affects offspring via an epigenetic mechanism involving REST/NRSF.2021
Author(s)
Yoshizaki Kaichi, Kimura Ryuichi, Kobayashi Hisato, Oki Shinya, Kikkawa Takako, Mai Lingling, Koike Kohei, Mochizumi Kentaro, Inada Hitoshi, Matsui Yasuhisa, Kono Tomohiro, Osumi Noriko
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Journal Title
EMBO Reports
Volume: 22(2)
Issue: 2
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Evolution of an mRNA transport mechanism in radial glial cells by acquisition of a unique zip code sequence in placental mammals2022
Author(s)
Kikkawa, T., Wakamatsu, Y., Inoue, YU., Suzuki, K., Inoue, T., Osumi, N.
Organizer
第44回 日本神経科学大会
Related Report
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[Presentation] Identification of FMRP target mRNAs in the developmental brain: FMRP might coordinate mTOR signaling during corticogenesis.2021
Author(s)
Kikkawa, T., Casingal, RC, Inoue, YU., Ebrahimiazar, S, Inada, H., Osumi, N.
Organizer
7th Congress of AsCNP
Related Report
Int'l Joint Research
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