Elucidation of the intracellular epigenetic modification and extracellular microenvironment regulating the development of the central nervous system
| Project/Area Number |
24300119
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
TAGA Tetsuya 東京医科歯科大学, 難治疾患研究所, 教授 (40192629)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | 神経幹細胞 / 発生・分化 / エピゲノム / 自己複製 / ニッチ / 神経科学 / 疾患モデルマウス / シグナル伝達 / 海馬 |
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| Outline of Final Research Achievements |
Gasc1 gene encodes a histone H3 lysine 9 (H3K9) demethylating enzyme, which we previously found is expressed in post-mitotic neurons in the mouse brain. We showed that GASC1 hypomorphic mutant mice exhibit mental disorder-like abnormal behaviors. In the present study, we have newly detected increased dendritic spine densities of the mutant hippocampal neurons. Electrophysiological studies on hippocampal slices have further demonstrated increased long-term potentiation. Further studies will enable us to discuss the cause of human neurological/psychiatric symptoms and future drug discoveries. We have also found that one of the ten-eleven translocation (TET) proteins, TET3, is involved in the timing of astrocyte development most likely through oxidization of the 5-methylcytosine.
We have also provided a novel molecular mechanism for NSC self-renewal in which one of the growth promoting signaling components, cyclin D1, which is induced by FGF2- and Wnts inhibits astrocyte differentiation.
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Report
(4 results)
Research Products
(49 results)
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[Journal Article] Sox17 haploinsufficiency results in perinatal biliary atresia and hepatitis in C57BL/6 background mice2013
Author(s)
Uemura. Mami., Ozawa A. Nagala T. Kurosawa K., Tsurukawa. K., Nobuhisa I., Taka T. Mara. K., Kudo, A., Kawakami. H., Saijoh. Y. Kurohmaru M. Kanai, Azuma. M., Kanai. Yoshiakira.
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Journal Title
Development
Volume: 140
Issue: 3
Pages: 639-648
DOI
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Peer Reviewed
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[Presentation] Epigenetic regulation of mouse neural stem cell differentiation and functional development2012
Author(s)
Tetsuya Taga, Tetsushi Kagawa, Norihisa Bizen, Yuhei Yamaguchi, Yasuhiro Kokubu, Satoko Hattori, Keizo Takao, Tsuyoshi Miyakawa, Johji Inazawa, Toshinobu Nakamura, Toru Nakano
Organizer
The 10^<th> Annual Meeting of International Society for Stem Cell Research
Place of Presentation
Yokohama
Related Report
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[Presentation] Sox-F family proteins have roles in the maintenance of immature phenotype of the hematopoietic cell clusters in the aorta-gonad-mesonephros region of mouse embryos2012
Author(s)
Ikuo Nobuhisa, Mitsujiro Osawa, Mami Uemura, Yoko Kishikawa, Maha Anani, Kaho Harada, Haruna Takagi, Akihiko Kudo, Masami Kanai-Azuma, Yoshiakira Kanai, Atsushi Iwama, Tetsuya Taga
Organizer
The 10^<th> Annual Meeting of International Society for Stem Cell Research
Place of Presentation
Yokohama
Related Report
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[Presentation] Regulation of mouse brain development by DNA and histone methylation: From molecular basis to cognitive, behavioral, and motor abnormalities in gene-manipulated model mice2012
Author(s)
Tetsuya Taga, Tetsushi Kagawa, Norihisa Bizen, Yuhei Yamaguchi, Yasuhiro Kokubu, Satoko Hattori, Keizo Takao, Tsuyoshi Miyakawa, Johji Inazawa, Toshinobu Nakamura, Toru Nakano
Organizer
The 35^<th> Annual Meeting of the Japan Neuroscience Society Symposium on Epigenetics and neuropsychiatric disorders
Place of Presentation
Nagoya(招待講演)
Related Report
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[Presentation] Hematopoietic cell clusters present in the aorta-gonad-mesonephros region exhibited long-term repopulating ability by Sox17-expression2012
Author(s)
Ikuo Nobuhisa, Mitsujiro Osawa, Mami Uemura, Yoko Kishikawa, Maha Anani, Kaho Harada, Haruna Takagi, Masami Kanai-Azuma, Yoshiakira Kanai, Atsushi Iwama, Tetsuya Taga
Organizer
The 35^<th> Annual Meeting of the Molecular Biology Society of Japan
Place of Presentation
Fukuoka
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[Book] カンデル神経科学2014
Author(s)
田賀哲也
Total Pages
1649
Publisher
メディカル・サイエンス・インターナショナル
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