Exogenous Reelin Modifies the Migratory Behavior of Neurons Depending on Cortical Location
Exogenous Reelin Modifies the Migratory Behavior of Neurons Depending on Cortical Location
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DOI：
10.1093/cercor/bht123
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发表时间：
2014-11-01
期刊：
影响因子：
3.7
通讯作者：
Tan, Seong-Seng
中科院分区：
文献类型：
--
作者：
Britto, Joanne M.;Tait, Karen J.;Tan, Seong-Seng
当生发区产生的投射神经元不能正确迁移到皮质板时，可能会出现皮质发育畸形。这一过程严重依赖于Reelin糖蛋白，当缺乏时会导致皮质层倒置和边界模糊。Reelin还具有其他功能，包括支持神经元迁移和维持它们的轨迹;然而，对于神经元的胶质纤维依赖性或非依赖性迁移的确切作用仍然存在争议。在这项研究中，我们希望测试的假设，迁移皮层神经元在不同水平的皮层壁有不同的反应，Reelin。我们将迁移穿过皮层壁的神经元暴露于外源性Reelin，并使用延时成像监测它们的迁移行为。我们的研究结果表明，在生发区，外源性Reelin延缓神经元迁移和改变他们的轨迹。这种行为与位于中间区（IZ）的神经元的反应相反，可能是因为Reelin受体在该区不表达。在reeler皮层，Reelin受体表达在IZ和暴露于外源性Reelin能够挽救迁移缺陷。这些研究表明，迁移的神经元有不等同的反应，取决于他们的位置在皮层壁内的Reelin。
Malformations of cortical development can arise when projection neurons generated in the germinal zones fail to migrate properly into the cortical plate. This process is critically dependent on the Reelin glycoprotein, which when absent leads to an inversion of cortical layers and blurring of borders. Reelin has other functions including supporting neuron migration and maintaining their trajectories; however, the precise role on glial fiber-dependent or -independent migration of neurons remains controversial. In this study, we wish to test the hypothesis that migrating cortical neurons at different levels of the cortical wall have differential responses to Reelin. We exposed neurons migrating across the cortical wall to exogenous Reelin and monitored their migratory behavior using time-lapse imaging. Our results show that, in the germinal zones, exogenous Reelin retarded neuron migration and altered their trajectories. This behavior is in contrast to the response of neurons located in the intermediate zone (IZ), possibly because Reelin receptors are not expressed in this zone. In the reeler cortex, Reelin receptors are expressed in the IZ and exposure to exogenous Reelin was able to rescue the migratory defect. These studies demonstrate that migrating neurons have nonequivalent responses to Reelin depending on their location within the cortical wall.