Ogawa M
Labolatory for Cell Culture Development, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, 351-0198 Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2000 Oct;20(4):169-74.
Corticohistogenesis follows highly regulated spatial and temporal patterns of cell proliferation, neuronal migration and neuronal differentiation to generate the characteristic cortical layers. We gained several insights into the mechanisms of the processes how a class of neurons attains an appropriate layer in developing neocortex. Using a neurological mutant mice reeler, we identified that the extracellular matrix protein Reelin that is specifically secreted from the Cajal-Retzius cells regulates the positioning of the cortical plate neurons. There has identified that Dab1 is one of the intracellular signaling components that respond to Reelin. Recently, three membrane proteins, apoER2, VLDLR and CNR are identified to bind Reelin. The double mutant--apoER2-/-; vldlr-/(-)--shows a phenotype indistinguishable from Reelin deficient mice. The CNRs are originally isolated through the interaction of their intracellular domain with Fyn, a member of the Src kinase family. The antibodies against Reelin or CNR disrupted Reelin-CNR binding. These three classes of membrane proteins are thought to act in concert as components of the Reelin receptor.
皮质组织发生遵循细胞增殖、神经元迁移和神经元分化高度有序的时空模式，以生成具有特征性的皮质层。我们对一类神经元如何在发育中的新皮质中到达合适的层的过程机制有了一些见解。通过使用神经学突变小鼠reeler，我们发现 Cajal-Retzius 细胞特异性分泌的细胞外基质蛋白 Reelin 调节皮质板神经元的定位。已确定 Dab1 是对 Reelin 作出反应的细胞内信号成分之一。最近，三种膜蛋白 apoER2、VLDLR 和 CNR 被确定为与 Reelin 结合。双突变体——apoER2-/-; vldlr-/-——表现出与 Reelin 缺陷小鼠无法区分的表型。CNRs 最初是通过其细胞内结构域与 Src 激酶家族成员 Fyn 的相互作用而分离出来的。抗 Reelin 或 CNR 的抗体破坏了 Reelin-CNR 结合。这三类膜蛋白被认为作为 Reelin 受体的成分协同作用。
