A MOLECULE REGULATING THE CELL PATTERNING IN CEREBRAL CORTEX.

我们的研究旨在寻找调节发育中的哺乳动物大脑皮层神经元层层排列的分子。这项工作之前使用了一种神经学突变的小鼠卷取器，在这种情况下，新皮质的组织发育异常，本质上导致皮质层的相对位置颠倒。对正常和突变小鼠大脑发育形态的比较分析表明，特征卷曲异常与早期产生的前板神经元和新产生的皮质板神经元之间的细胞-细胞相互作用缺陷有关。我们假设，由卷轴基因编码的一个独特的分子可能参与了这种相互作用。我们已经成功地研制出一种抗体CR-50，它可以探测正常但不存在于卷轴中的一种独特的抗原。最近发现，CR-50识别由Reeler基因编码的Reelin的N端。利用这种抗体，我们观察到Reelin与活体Cajal-Retzius神经元的细胞表面特异性结合，Cajal-Retzius神经元是板前神经元之一。CR-50在体内和体外对大脑皮层细胞排列的干扰结果表明，Reelin是为大脑皮层发育中的新皮质细胞提供适当排列和定位的表面决定因素之一。我们进一步揭示了Reelin在小脑发育过程中浦肯野细胞排列成不同的一层中起着至关重要的作用。此外，在体内，CR-50还破坏了海马体Ammon角内的锥体细胞。这些观察结果表明，在中枢神经系统发育过程中，Reelin在神经元的正确排列中起着关键作用。

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.