Regulation of expansion phase of neural stem cells by Hmga2 and PcG
| Project/Area Number |
15K06947
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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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| Research Field |
Molecular biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Kishi Yusuke 東京大学, 大学院薬学系研究科(薬学部), 講師 (00645236)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 神経幹細胞 / 増殖期 / Hmga2 / ポリコーム / クロマチン / HMGA / 遺伝子導入法 |
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| Outline of Final Research Achievements |
Neurons and glial cells in the central nervous system are derived from neural stem/progenitor cells (NPCs). During the early stage of mouse neocortical development, NPCs proliferate symmetrically to increase their pool size (the expansion phase). They then switch to the asymmetric mode of division and sequentially generate neurons (the neurogenic phase) and glial cells (the gliogenic phases). The transition of the expansion-to-neurogenic phase is critical for determining the number of NPCs and thus should be strictly regulated. However, it remains unclear how the timing of this transition is regulated and how its dysregulation influences brain organogenesis, partly due to the difficulty of genetic manipulation of NPCs during the expansion phase. In this study, we developed a new method to manipulate genes-of-interest in NPCs during the expansion phase, and found a mechanism to regulate the fate transition of NPCs.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって開発した新規遺伝子導入法は、「幹細胞がどのようにして分化細胞を産生し始めるのか」という幹細胞生物学における根源的な問いに答えるツールとして利用できる。特に、ES細胞のような培養細胞ではなく、生体内の神経幹細胞でそれを検討できることが非常に重要である。
また近年の研究から、神経幹細胞の増殖期からニューロン分化期への転換の異常が、結果として成人における自閉症などの精神疾患の原因になることが示唆されてきている。新規遺伝子導入法を活用することで、その因果関係や制御メカニズムを明らかにし、増殖期からニューロン分化期への転換異常による様々な疾患の原因究明、治療法開発につながる可能性がある。
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Report
(5 results)
Research Products
(30 results)
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[Journal Article] The PDK1-Akt Pathway Regulates Radial Neuronal Migration and Microtubules in the Developing Mouse Neocortex2016
Author(s)
Itoh, Y., Higuchi, M., Oishi, K.,Kishi, Y., Okazaki, T., Sakai, H., Miyata, T., Nakajima, K., Gotoh, Y.
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Journal Title
PNAS.
Volume: 113(21)
Issue: 21
Pages: 2955-64
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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