Molecular mechanisms of defective cortical histogenesis in the cerebellar development.

神经元-胶质细胞相互作用在神经发育过程中的皮质结构的组织发生中起着重要作用，这种相互作用的遗传障碍可能导致皮质发生缺陷。在这项研究中，在小脑发育过程中的神经元-胶质细胞的相互作用进行了检查，在正常和reeler突变小鼠，以阐明有缺陷的皮质形成的机制。神经元-胶质细胞粘附分子tenascin的表达被用作发育中小脑中胚胎放射状胶质细胞和新生儿Bergmann胶质细胞的标记物。非放射性原位杂交组织化学研究肌腱蛋白基因表达揭示了放射状胶质细胞胞体的迁移模式，肌腱蛋白免疫组化代表了小脑发育过程中放射状胶质细胞过程的动态变化。Purkinje细胞沿着腱生蛋白免疫反应阳性的放射状胶质突起迁移后，放射状胶质细胞从脑室区放射状迁移到皮质，从脑室区延伸到软脑膜的放射状胶质突起向皮质缩回。这些放射状胶质细胞在出生后小脑中占据与Bergmann胶质细胞相对应的位置，并显示GFAP免疫反应性沿着tenascin基因的表达。在小脑发育的reeler小脑，伯格曼胶质细胞体的迁移受阻的模式类似于位于皮质下的浦肯野细胞。皮质内Bergmann胶质细胞突起和胞体的排列也有缺陷。只有有限数量的Bergmann神经胶质细胞的过程与浦肯野细胞在皮质对齐。这些研究结果表明，有缺陷的皮质形成在reeler小脑是由于缺陷的Bergmann胶质细胞形态发生和神经元-胶质细胞的相互作用的障碍，在接触指导浦肯野细胞迁移的放射状胶质过程。

Neuron-glia interactions play important roles in the histogenesis of cortical structure during neural development, and the genetic disorders of such interactions may lead to the defective corticogenesis. In this study, neuron-glia interactions during cerebellar development were examined both in the normal and reeler mutant mice in order to elucidate the mechanisms of defective cortical formation. Expression of tenascin, a neuron-glia adhesion molecule, was used as the marker for embryonic radial glia and neonatal Bergmann glia in the developing cerebellum. Tenascin gene expression as examined by non-radioactive in situ hybridezation histochemistry revealed the mode of migration of the somata of radial glia, and tenascin-immunohistochemistry represented the dynamics of radial glial processes during cerebellar development. Radial glial somata migrated radially from the ventricular zone to the cortex and radial glial processes extending from ventricular zone to pia mater retracted towards the cortex after the contact guidance of Purkinje cell migration along tenascinimmunoreactive radial glial processes. These radial glia occupied a position corresponding to Bergmann glia in the postnatal cerebellum and showed GFAP-immunoreactivity along with the expression of tenascin gene. In the cerebellar development of the reeler cerebellum, the migration of Bergmann glial somata was obstructed in the pattern similar to subcortically situated Purkinje cells. The arrangement of both the processes and somata of Bergmann glia in the cortex was also defective. Only limited number of Bergmann glial processes were associated with Purkinje cells which were aligned in the cortex. These findings suggest that the defective cortical formation in the reeler cerebellum is due to the defect of Bergmann glial morphogenesis and the disorder of neuron-glia interactions during the contact guidance of Purkinje cell migration by radial glial processes.