Project/Area Number |
08458247
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Nerve anatomy/Neuropathology
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Research Institution | KOCHI MEDICAL SCHOOL |
Principal Investigator |
OGAWA Masaharu KOCHI MEDICAL SCHOOL,DEPARTMENT OF PHYSIOLOGY,ASSOCIATE PROFESSOR, 医学部, 助教授 (50111951)
|
Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Kazunori INSTITUTE FOR PHYSICAL AND CHEMICAL RESEARCH (RIKEN), MOLECULAR NEUROBIOLOGY LAB, ライフサイエンス筑波研究センター・分子神経生物研究室, 研究員 (90280734)
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Project Period (FY) |
1996 – 1997
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Project Status |
Completed (Fiscal Year 1997)
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Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
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Keywords | CEREBRUM / CORTICOHISTOGENESIS / REELER MUTANT MOUSE / CR-50 / REELIN / CEREBELLUM / HIPPOCAMPUS / hippocampus / cerebellum / リーリン / リーラーミュータントマウス / 大脳皮質 / Cajal-Retzius細胞 / preplate |
Research Abstract |
Our research is aimed to find moleculse that regulate the laminar alignment of neurons in the developing mammalian cerebral cortex. The work was preceded using a neurological mutant mouse reeler, in which the histological organization of the neocortex develops abnormally and essentially results in an inversion of the relative positions of the cortical layrs. The comparative analysis of the morphology of developing cerebrum in normal and mutant mice indicated that the characteristic reeler abnormality couples with the faulty of cell-cell interactions between the early generated preplate and the lately generated cortical plate neurons. We hypothesized that a distinct molecule encoded by the reeler gene may be involved in this interaction. We have succeeded to raise an antibody CR-50 that probed a distinct antigen present in normal but not in reeler. It was lately revealed that CR-50 recognizes the N-terminal of Reelin, the protein encoded by reeler gene. Using this antibody we observed that the Reelin associates specifically with the cell surfaces of living Cajal-Retzius neurons, one of the neurons of preplate. The results of disturbance of cortical cell arrangement in vivo and in vitro with CR-50 make it evident that the Reelin is one of surface determinants that provides for cortical neorons to align and orient themselves properly in developing neocortex. We further revealed that Reelin plays an essential role in the arrangement of Purkinje cells into a distinct layr in developing cerebellum. Furthermore, the pyramidal cells in Ammon horn of hippocampal body are disrupted in vivo by CR-50. These observations indicate that the Reelin plays a critical role in proper arrangement of neurons in developing CNS.
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