筛选神经发育和神经干细胞微环境中血管细胞粘附分子VCAM-1的相互作用分子的研究

项目名称： 筛选神经发育和神经干细胞微环境中血管细胞粘附分子VCAM-1的相互作用分子的研究

项目编号： No.31200798

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经、认识与心理学

项目作者： 胡晓玲

作者单位： 清华大学

项目金额： 25万元

中文摘要： 理解大脑的正常发育机制有助于我们理解先天发育性神经疾病和神经退行性疾病的发病机制。血管细胞粘附分子VCAM-1是一种表达在激活的血管内皮细胞表面，介导白细胞粘附的分子。我们前期研究发现VCAM-1表达在发育大脑的脑室区和脑室下区。在成年小鼠大脑，VCAM-1只表达在SVZ区的细胞中。VCAM-1的这种特定的细胞表达模式与神经干细胞的表达模式高度一致。运用RNA干扰技术敲减内源性VCAM-1，我们发现神经干细胞的自我更新被抑制。由于小鼠神经发育过程中没有检测到VCAM-1受体VLA4的表达，因此我们推测，在神经发育和成年SVZ区，还存在其他与VCAM-1相互作用分子。本项目拟通过对发育过程和成年大脑SVZ区的组织进行免疫共沉淀，结合蛋白质组学分析技术，筛选出与VCAM-1相互作用的分子，并进行验证。对VCAM-1在神经干细胞发育或神经干细胞微环境中的信号传导通路进行深入研究。

中文关键词： VCAM1；神经干细胞；微环境；GSK3β；自我更新

英文摘要： Understanding the mechanisms of neural development would help us understand the pathogenesis of developmental brain disorders and neurodegenerative diseases. Vascular cell adhesion molecule (VCAM-1) is a cell adhesion molecule expressed on the membrane surface of activated vascular endothelial cells. When binding with surface receptor VLA4 (α4 integrin) of leukocyte, VCAM-1 would mediate endothelial cell deformation and leukocyte migration. In the central nervous system, neural stem cells and progenitor cells are situated in the developing ventricular zone (VZ) and subventricular zone (SVZ), and a subset of Type B astrocytes continue to produce neurons in the adult SVZ lining the striatal side of the lateral ventricle. Our previous study found that VCAM-1 is highly expressed in the developing ventricular zone of the forebrain and a subset of Type B cells in the SVZ in the adult neurogenic niche. The expression of VCAM-1 gradually decreases as the number of neural progenitor cells decrease during development but persists in adult SVZ niche, indicating VCAM-1 expression pattern is highly correlated with development of neural stem cells. Knocking down of endogenous VCAM-1 with shRNA in neural stem cells leads to suppressed self-renewal in neurosphere assay, suggesting VCAM-1 plays an important role in neural stem c

英文关键词： VCAM1；neural stem cells；niche；GSK3β；self-renewal