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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 maturation and maturation of neural stem cells in the subventricular zone (SVZ) of mice and the process of migration to the olfactory bulb (OB) along the tangential line of the rostral flow migration (RMS), especially the effects of Reelin on cell migration and cell differentiation. Methods Fifty mice of wild-type (WT) mice and 23 mice of homozygous reeler mice were used to study the effects of Nissl staining, immunofluorescence staining, ink perfusion and electron microscopy Marked and observed the relationship between neural stem cells, glial cells and angiogenesis in mouse brain, and compared the RMS development of mice in both groups. RESULTS: From the late embryo to the early stage of embryo, a large number of glial cells, neural stem cells and vascular network were distributed in SVZ, and they were interconnected to form niche which incubated with SVZ neural stem cells. After neural stem cells were incubated in niche, they could enter RMS, The tangents migrate to the olfactory bulb, reach the olfactory bulb and then transform into radial migration, and differentiate into various neurons to integrate into the olfactory bulb. During the migration of RMS, the radial glial cells cooperate with the blood vessels to provide scaffold guidance; the reeler mice can also form RMS, but the morphological changes, mainly in the olfactory bulb at the loss of regularity of neural stem cells were scattered distribution. CONCLUSION: Niche, a subventricular zone, is the main source of neural stem cells. Vascular collateral radial glial cells provide a scaffold for neural stem cells in RMS. As an important signal for regulating cell migration, Reelin can influence the development of blood vessels through its interaction , A loss of Reelin leads to a dysregulation of the radial migration of neural stem cells at the olfactory bulb.