Hartfuss Eva, Förster Eckart, Bock Hans H, Hack Michael A, Leprince Pierre, Luque Juan M, Herz Joachim, Frotscher Michael, Götz Magdalena
Max-Planck-Institute of Neurobiology, Neuronal Specification, Am Klopferspitz 18a, D-82152 Martinsried, Germany.
Development. 2003 Oct;130(19):4597-609. doi: 10.1242/dev.00654.
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.
放射状胶质细胞除具有星形胶质细胞的特性外，其特征还在于有从脑室区延伸至软脑膜表面的长放射状突起，这是神经元放射状迁移的关键特征。然而，调节这种特征性形态的分子信号在很大程度上尚不清楚。我们发现分泌分子reelin在放射状胶质细胞突起的形成中起重要作用。我们描述了在reeler突变小鼠的皮质中，缺乏reelin时，具有长放射状突起的脑室区细胞显著减少。这些缺陷与脑脂质结合蛋白（Blbp）含量的降低相关，且仅在大脑皮质中检测到，而在reeler小鼠的基底神经节中未检测到。相反，体外添加reelin可增加皮质而非基底神经节的放射状胶质细胞的Blbp含量和突起延伸。通过荧光激活细胞分选分离放射状胶质细胞表明，这些效应是由于reelin直接作用于放射状胶质细胞。我们进一步证明这种信号传导需要Dab1，因为在Dab1基因敲除小鼠中，添加reelin后Blbp含量并未增加。综上所述，这些结果揭示了reelin信号对放射状胶质细胞的新作用，这对于以区域特异性方式调节其Blbp含量和特征性形态至关重要。
