Molecular mechanisms of forebrain morphogenesis
| Project/Area Number |
18590168
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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 |
General anatomy (including Histology/Embryology)
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| Research Institution | Kyoto University |
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Principal Investigator |
ISHIBASHI Makoto Kyoto University, Graduate School of Medicine, Department of Anatomy and Developmental Biology, Associate Professor (30232341)
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| Co-Investigator(Kenkyū-buntansha) |
SHIOTA Kohei Kyoto University, Graduate School of Medicine, Department of Anatomy and Developmental Biology, Professor (80109529)
MIURA Takashi Kyoto University, Graduate School of Medicine, Department of Anatomy and Developmental Biology, Assistant Professor (10324617)
才津 浩智 京都大学, 医学研究科, 助手 (40402838)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | diencephalon / nuclei / positional information / signal / regulation of gene expression / cerebral cortex / cell cycle / layer formation / 前脳 / 形態形成 / Fgf / Sonic hedgehog / Lhx |
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| Research Abstract |
The aim of this research is to elucidate molecular mechanisms of forebrain (diencephalon and telencephalon) development. In the diencephalon, there are many different nuclei in distinct positions. How these positions are determined has not been understood. To clarify the mechanisms, we examined expression patterns of Lhx1and Lhx9 in the developing chick diencephalon. Dynamic expression patterns were observed at the patterning stages. Previous studies suggested that these genes play important roles in differentiation of diencephalic nuclei. The above results led us to examination of regulatory mechanisms of Lhx1/9 genes. We hypothesized that some molecules provide the tissue with positional information. Candidate molecules are Sonic hedgehog which is expressed in the ventral region and Wnt which is expressed in the dorsal region. Since Lhx1 is expressed mainly in the ventral region, Sonic hedgehog likely regulates Lhx1 expression. In fact, ectopic expression of Sonic hedgehog induced ectopic Lhx1 expression in the diencephalon. Similarly, Wnt from the dorsal region seemed to regulate Lhx9 expression. Overexpression of Wnt3a led to expansion of the Lhx9 expression domain. FGF15/19 is also expressed in the dorsal region. Overexpression of FGF15 up-regulated Lhx9 as well.
To elucidate the roles of Sonic hedgehog in corticogenesis in the mouse cerebrum, we analyzed the dorsal telencephalon-specific knock-outs. These mutants showed abnormal cell cycle kinetics and survival of the neural stem/progenitor cells. Also, positions of differentiated neurons in the cerebral cortex were affected.
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Report
(3 results)
Research Products
(30 results)
