| Project/Area Number |
13308047
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | The Institute of Physical and Chemical Research (RIKEN) |
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Principal Investigator |
FURUICHI Teiichi The Institute of Physical and Chemical Research (RIKEN), Laboratory for Molecular Neurogenesis, Laboratory Head, 分子神経形成研究チーム, チームリーダー (50219094)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUKI Tohru The Institute of Physical and Chemical Research (RIKEN), Laboratory for Molecular Neurogenesis, Researcher, 分子神経形成研究チーム, 研究員 (90332329)
SATO Akira The Institute of Physical and Chemical Research (RIKEN), Laboratory for Molecular Neurogenesis, Researcher, 分子神経形成研究チーム, 研究員 (60321767)
YOSHIKAWA Fumio The Institute of Physical and Chemical Research (RIKEN), Laboratory for Molecular Neurogenesis, Researcher, 分子神経形成研究チーム, 研究員 (70342871)
SHOJI Satoshi The Institute of Physical and Chemical Research (RIKEN), Laboratory for Molecular Neurogenesis, Researcher, 分子神経形成研究チーム, 研究員 (10333353)
TOMOMURA Mineko The Institute of Physical and Chemical Research (RIKEN), Laboratory for Molecular Neurogenesis, Researcher, 分子神経形成研究チーム, 研究員 (30217559)
高野 りや 理化学研究所, 分子神経形成研究チーム, 研究員 (80332328)
中村 浩 理化学研究所, 分子神経形成研究チーム, 研究員 (70321792)
白石 陽子 理化学研究所, 分子神経形成研究チーム, 基礎科学特別研究員 (50311345)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥46,410,000 (Direct Cost: ¥35,700,000、Indirect Cost: ¥10,710,000)
Fiscal Year 2003: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2002: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2001: ¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000)
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| Keywords | cerebellum / Cupidin / Homer / CAPS2 / glutamate receptor / postsynaptic density / neurotrophin / transcriptome / gene expression / 生後発達 / CPAS2 / データベース / マイクロアレイ / シナプス形成 / ディファレンシャルディスプレイ / 顆粒細胞 / プルキンエ細胞 / Gene Chip / シナプス / NMDA受容体 / 組換えウイルスベクター / グルタミン酸 |
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| Research Abstract |
1.By the differential display, microarray, and GeneChip analysis approaches, we explored the gene expression profiles specific to the postnatal developmental stages of mouse cerebellum on a genome-wide basis. In addition, we revealed the spatio-temporal expression patterns of specific genes by RT-PCR and in situ hybridization methods. Integrating all these lines of gene expression information, we have generated the "Cerebellar Development Transcriptome database". By this study, we have succeeded in cloning of many candidates for novel genes responsible for brain development as follows.
2.We showed that dendritic clustering and synaptic targeting of Cupidin/Homer, an adaptor protein at postsynaptic density (PSD), coincides those of glutamate receptor-related proteins NR2B and PSD-95 during development of hippocampal neurons, that Cupidin act s as a mobile adaptor in cerebellar granule cells in an activity-dependent manner, and that the Homer family members have differential cellular distributions in developing mouse brains.
3.We cloned CAPS2, a paralog of CAPS that regulates Ca2+-dependent exocytosis of secretory granules. CAPS2 was localized to vesicular structures, in which neurotrophins BDNF and NT-3 are included, in parallel fiber terminals of cerebellar granule cells. The overexpression of exogenous CAPS2 in primary cultured granule cells augmented NT-3 release in a depolarization-dependent manner, resulting in promoting survival of Purkinje cells. These data indicate that CAPS2 is a molecule that regulates activity-dependent release of neurotrophins that are indispensable for differentiation and survival of cerebellar neurons.
4.We analyzed the structure, function, and brain expression of three genes related to protein phsophorylation (apoptosis activity-related tyrosine kinase AATYK, novel Ser/Thr kinase Ebr, and tyrosine kinase adaptor Cas) and a gene encoded a novel myelin paranodal loop protein.
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