Reelin signaling directly affects radial glia morphology and biochemical maturation
Reelin signaling directly affects radial glia morphology and biochemical maturation
复制标题
DOI：
10.1242/dev.00654
复制
发表时间：
2003-10-01
期刊：
影响因子：
4.6
通讯作者：
Götz, M
中科院分区：
文献类型：
--
作者：
Hartfuss, E;Förster, E;Götz, M
除了星形胶质细胞的特性外，放射状胶质细胞的特征是从脑室区域延伸到软膜表面的长径向突起，这是神经元放射状迁移的关键特征。然而，调节这种特征形态的分子信号在很大程度上是未知的。我们展示了分泌分子reelin在建立放射状胶质细胞突起中的重要作用。我们描述了在卷绕突变小鼠的大脑皮质中没有卷曲蛋白的情况下，长放射状突起的脑室带细胞显著减少。这些缺陷与脑脂结合蛋白(BLBP)的含量降低有关，并且仅在大脑皮层中检测到，而在Reeler小鼠的基底节中没有检测到。反之，体外加入Reelin可增加皮质放射状胶质细胞的BBP含量和突起伸展，但不增加基底节的BBP含量。用荧光激活细胞分选法分离放射状胶质细胞表明，这些作用是由于Reelin直接向放射状胶质细胞传递信号。我们可以进一步证明这种信号需要Dab1，因为在Dab1(-/-)小鼠中没有发生在Reelin增加时BBP的增加。综上所述，这些结果揭示了Reelin信号对放射状胶质细胞的一个新的作用，该作用对于以区域特有的方式调节其BlBP含量和特征形态至关重要。
Radial glial cells are characterized, besides their astroglial properties, by long radial processes extending from the ventricular zone to the pial surface, a crucial feature for the radial migration of neurons. The molecular signals that regulate this characteristic morphology, however, are largely unknown. We show an important role of the secreted molecule reelin for the establishment of radial glia processes. We describe a significant reduction in ventricular zone cells with long radial processes in the absence of reelin in the cortex of reeler mutant mice. These defects were correlated to a decrease in the content of brain lipid-binding protein (Blbp) and were detected exclusively in the cerebral cortex, but not in the basal ganglia of reeler mice. Conversely, reelin addition in vitro increased the Blbp content and process extension of radial glia from the cortex, but not the basal ganglia. Isolation of radial glia by fluorescent-activated cell sorting showed that these effects are due to direct signaling of reelin to radial glial cells. We could further demonstrate that this signaling requires Dab1, as the increase in Blbp upon reelin addition failed to occur in Dab1(-/-) mice. Taken together, these results unravel a novel role of reelin signaling to radial glial cells that is crucial for the regulation of their Blbp content and characteristic morphology in a region-specific manner.