Frotscher Michael, Haas Carola A, Förster Eckart
Anatomisches Institut, Universität Freiburg, Albertstrasse 17, D-79104 Freiburg, Germany.
Cereb Cortex. 2003 Jun;13(6):634-40. doi: 10.1093/cercor/13.6.634.
Reelin, synthesized and secreted by Cajal-Retzius (CR) cells in the marginal zone of the cortex, is an extracellular matrix protein important for the development of cortical layers. In reeler mutant mice lacking Reelin, there are severe malformations of neocortical and hippocampal lamination. It has been assumed that Reelin acts as a stop signal for migrating neurons. Here we show, by using the dentate gyrus as a model in in vivo studies and in vitro assays, that Reelin exerts its effects, at least in part, by acting on the radial glial scaffold required for neuronal migration. Migration defects of dentate granule cells, reminiscent of those seen in reeler mutants, are observed in tissue from patients with temporal lobe epilepsy (TLE). The extent of granule cell dispersion in TLE was found to be inversely correlated with the number of reelin mRNA synthesizing CR cells and reelin mRNA expression as revealed in quantitative RT-PCR studies. These findings show that the Reelin signaling pathway is essential for the correct positioning of human hippocampal neurons and that a Reelin deficiency is involved in the pathological changes associated with epilepsy.
Reelin由皮质边缘区的Cajal-Retzius（CR）细胞合成并分泌，是一种对皮质层发育至关重要的细胞外基质蛋白。在缺乏Reelin的reeler突变小鼠中，新皮质和海马分层存在严重畸形。人们认为Reelin作为迁移神经元的停止信号。在这里，我们通过使用齿状回作为体内研究和体外试验的模型表明，Reelin至少部分地通过作用于神经元迁移所需的放射状胶质支架来发挥其作用。在颞叶癫痫（TLE）患者的组织中观察到齿状颗粒细胞的迁移缺陷，这让人联想到在reeler突变体中看到的情况。定量逆转录聚合酶链反应研究显示，TLE中颗粒细胞分散的程度与合成Reelin mRNA的CR细胞数量和Reelin mRNA表达呈负相关。这些发现表明，Reelin信号通路对于人类海马神经元的正确定位至关重要，并且Reelin缺乏与癫痫相关的病理变化有关。
