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A MOLECULE REGULATING THE CELL PATTERNING IN CEREBRAL CORTEX.

调节大脑皮层细胞模式的分子。

基本信息

批准号：
08458247
负责人：
OGAWA Masaharu
金额：
$ 1.22万
依托单位：
KOCHI MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

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.

我们的研究旨在寻找调节哺乳动物大脑皮层发育中神经元层排列的分子。这项工作之前使用神经突变小鼠卷轴，其中新皮质的组织学组织发育异常，基本上导致皮质层的相对位置倒置。对正常和突变小鼠大脑发育形态学的比较分析表明，特征性的reeler异常与早期产生的前板神经元和晚期产生的皮质板神经元之间的细胞-细胞相互作用缺陷相耦合。我们假设，一个独特的分子编码的reeler基因可能参与这种相互作用。我们已经成功地提出了一个抗体CR-50，探测一个独特的抗原存在于正常的，但不是在卷轴。最近发现CR-50识别由reeler基因编码的蛋白Reelin的N-末端。使用这种抗体，我们观察到，Reelin与活的Cajal-Retzius神经元（preplate神经元之一）的细胞表面特异性相关。用CR-50在体内和体外扰乱皮层细胞排列的结果表明，Reelin是在发育中的新皮层中提供皮层新细胞正确排列和定向的表面决定因素之一。我们进一步揭示了Reelin在小脑发育过程中对浦肯野细胞排列成一个独特的层起着至关重要的作用。此外，CR-50在体内可破坏海马体阿蒙角的锥体细胞。这些观察结果表明，Reelin在发育中的CNS神经元的正确排列中起着关键作用。