Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants |
|Research Institution||Keio University |
UYEMURA Keiichi Keio University School of Medicine Professor, 医学部, 教授 (90049792)
ASOU Hiroaki Tokyo Metropolitan Institute of Gerontology Head, 室長研究職 (30104160)
OKAMOTO Hitoshi Brain Science Institute, RIKEN Laboratory Head, 脳科学総合研究センター, チームリーダー (40183769)
HUN Chunxi Keio University School of Medicine Instructor, 医学部, 助手 (40306832)
TODA Masahiro Keio University School of Medicine Instructor, 医学部, 助手 (20217508)
YAZAKI Takahito Keio University School of Medicine Assistant Professor, 医学部, 専任講師 (80200484)
竹内 京子 慶應義塾大学, 医学部, 助手 (80116954)
石井 加代子 慶應義塾大学, 医学部, 助手 (30193246)
村上 健一 慶應義塾大学, 医学部, 助手 (30239488)
武田 泰生 慶應義塾大学, 医学部, 助手 (60245462)
|Project Period (FY)
1996 – 1998
Completed (Fiscal Year 1998)
|Budget Amount *help
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥2,800,000 (Direct Cost: ¥2,800,000)
|Keywords||cell adhesion proteins / L1 / Pax6 / phosphacan / herpes simplex virus vector / Schwann cells / neuregulin / Charcot-Marie-Tooth disease / 神経再生 / 細胞接着蛋白 / L1蛋白 / フォスファカン / 末梢神経ミエリン蛋白 / 変異型ヘルペスベクター / グリア成長因子 / アストロサイト|
We studied on physiological roles of several cell adhesion proteins during development and regeneration of the nervous system.
1) Complete L1 is expressed exclusively in neurons, but its truncated isoform is found in non-neuronal cells. We suggest that phosphorylation of the serine residue is important for cell migration.
2) By subtilisin-like proprotein convertases, 200kD L1 is cleaved to l4OkD and 8OkD molecules, resulting its functional changes during development.
3) By analysis of Pax6 deficient mutant mice, we indicate that Pax6 regulates central steps in forebrain development, especially in the formation of thalamocortical pathway.
4)Coordinate expression of L1 in the horizontal axons and phosphacan in the mesencephalic dopaminergic neurons is correlated with the neuronal migration.
5) The astrocytes in primary culture, which expressed L1 by transfection of L1cDNA with a defective herpes simplex virus vector, showed homophilic cell adhesion and promotion of neurite extension and neuro
6) We found a new flame shift mutation of L1 gene in Japanese family of hereditary hydrocephalus and abnormal expression of Lie in human disorders of neuronal migration.
7) CD44H was expressed continuously from migrating neural crest cells to myelinating Schwann cells, suggesting utility of CD44H as a Schwann cell marker. At the premyelinating stage, a significant number of Schwann cells dies by apoptosis and the apoptosis was suppressed by the addition of neuregulins or by the adhesion to substratum. Multiple isoforms of neuregulin are expressed in developing rat dorsal root ganglia.
8) We developed the useful method to purify PG and PASII/PMP22 proteins by immobilized metal affinity chromatography for crystallization. A new mutation of the P0 gene was found in patients with Charcot-Marie-Tooth disease type lB by screening of the P0 gene by heteroduplex analysis.
9) Impaired expression of L1 was observed in the extrinsic nerve fibers in colon locus of Hirschsprung's disease. Less