| Project/Area Number |
22570202
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Developmental biology
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| Research Institution | Tohoku University |
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Principal Investigator |
KATSUYAMA Yu 東北大学, 大学院・医学系研究科, 講師 (10359862)
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| Co-Investigator(Kenkyū-buntansha) |
TERASHIMA Toshio 神戸大学, 大学院・医学研究科, 教授 (20101892)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 細胞分化 / 神経分化 / シグナル伝達 / 転写調節 / ニューロン分化 / 脳形態形成 / Sbno1 |
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| Research Abstract |
Maintenance of the neural stem cells and neuronal differentiation are precisely regulated during brain development, and molecular mechanisms involved in this regulation have not been fully understood yet. We found that the homologue of Sbno1 is required for neuronal differentiation by gene-knockdown experiments in zebrafish. We next examined in vivo function of Sbno1 during mouse brain development. We examined expression pattern of Sbno1 protein using anti-Sbno1 antibodies. In the developing cerebral cortex, Sbno1 was observed in the nucleus of differentiating neurons near the marginal zone, and also in the cytoplasm of the cells in basal side including the ventricular zone. To achieve gene knockout specifically in the dorsal forebrain, we constructed Sbno1-floxed mice, and crossed these to Emx1Cre transgenic strain that expresses Cre-recombinase in the developing dorsal forebrain. Sbno1 conditional knockout (cKO) mice had a very thin cerebral cortex, when examined at postnatal day 10. Proliferation of the neural stem cells was slightly in the E12.5 Sbno1 cKO. We observed intermingling of the neural stem cells and differentiating neurons from E12 to E14 in Sbno1 cKO embryos, suggesting premature differentiation of the neurons. Cell death detected by TUNEL method and active caspase3 or p53 immunoreactivity was robustly occurred in cKO cortex. Cell death was observed in the Tuj1 positive differentiating neurons, but not in the Pax6 positive neural stem cells. These observations suggest that Sbno1 is essential for not only maintenance of the neural stem cells but also survival of differentiating neurons.
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