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Reelin调节小鼠喙端迁移流发育的形态学观察
Morphological study of Reelin regulation on the development of rostral migratory stream in the mouse
目的 探讨小鼠室管膜下区（SVZ）的神经干细胞孵育成熟以及沿喙端迁移流（RMS）切线迁移至嗅球(OB)的过程，尤其是Reelin对细胞迁移和细胞分化的影响。方法 选用野生型（WT）小鼠50只和纯合reeler小鼠23只胚胎16 d至生后90 d的各年龄点小鼠大脑，应用尼氏染色、免疫荧光染色、墨汁灌注及电子显微镜技术标记并观察小鼠大脑的神经干细胞、胶质细胞以及血管发生之间的相互关系，比较两组小鼠RMS的发育情况。结果 胚胎后期至出生早期，在SVZ分布着大量的胶质细胞、神经干细胞和血管网，它们相互联系构成SVZ神经干细胞孵育的血管龛(niche)；神经干细胞在niche中孵育成熟后可以进入RMS，切线迁移至嗅球，到达嗅球后转变为放射状迁移，分化为各种神经元整合入嗅球；神经干细胞在RMS的迁移过程中，放射状胶质细胞协同血管为其提供支架引导；reeler小鼠也能形成RMS，但形态有所改变，主要在嗅球处，神经干细胞失去规律排列，呈散乱分布。结论 室管膜下区的niche是神经干细胞的主要来源；血管协同放射状胶质细胞为RMS中的神经干细胞提供支架引导作用；作为调节细胞迁移的重要信号，Reelin可以通过其交互作用影响血管的发育，Reelin缺失导致嗅球处神经干细胞放射状迁移的转变障碍。
Objective To investigate the differentiation of neural stem cells in the subventridular zone (SVZ) and neural migration along the the rostral migratory stream (RMS) into the olfactory bulb（OB), particularly, Reelin’s effect on the neural differentiation and migration in RMS. Methods Wild type mice (50 cases) and reeler mice (23 cases) from E16 (embryonic day 16) to P90 (postnatal day 90) were used for Nissl staining, immunofluorescent labeling, ink perfusion and ultrastructure observation to visualize neural stem cells, the radial glial cells and vasulature in neocortex and RMS. The development of RMS in two groups was compared. Results In embryonic days and early postnatal period, vascular niches in the SVZ consisted of neurons, glial cells, neural stem cells and vascular vessel which provided a ideal microenvironment for the differentiation and mturation of neural stem cells. After maturation in the vascular niche, the neural stem cells started to migrate tangentially along RMS toward olfactory bulb with the chain-guidable pattern along both glial and vascular scaffold. After entering in OB, the migrating pattern translated into the radial migration, and these cells differentiated into various neuron in olfactory bulb. In general, RMS’s development, neural stem cell differentiation and cell migration in reeler mice were similar to the wild type, howover, the distribution of vasculature in cortex and RMS was disordered, and the migrating cells often concentrated in olfactory bulb densely and scatteredly. Conclusion Niche in subventricular zone is the main sources of neural stem cells, and both vasculature and radial glia and acts as a scaffold for the migration of neural stem cells in RMS. As an important signal for cell migration, Reelin can affect the development of blood vessels and cell migration in RMS. Without Reelin, the cell migration in RMS will be blocked.
喙端迁移流 / Reelin / 嗅球 / 血管 / 免疫荧光 / 小鼠
Rostral migratory stream / Reelin / Olfactory bulb / Vessel / Immunofluorescence / Mouse
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国家自然科学基金;河南大学优青项目;河南大学种子基金项目
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