Howard Florey Institute, Florey Neuroscience Institutes, Parkville, Victoria 3010, Australia.
Cereb Cortex. 2011 May;21(5):1018-27. doi: 10.1093/cercor/bhq168. Epub 2010 Sep 16.
The Reelin signaling pathway is essential for proper cortical development, but it is unclear to whether Reelin function is primarily important for cortical layering or neuron migration. It has been proposed that Reelin is perhaps required only for somal translocation but not glial-dependent locomotion. This implies that the location of neurons responding to Reelin is restricted to the outer regions of the cortical plate (CP). To determine whether Reelin is required for migration outside of the CP, we used time-lapse imaging to track the behavior of cells undergoing locomotion in the germinal zones. We focused on the migratory activity in the ventricular/subventricular zones where the first transition of bipolar to multipolar migration occurs and where functional Reelin receptors are known to be expressed. Despite Reelin loss, neurons had no difficulty in undergoing radial migration and indeed displayed greater migratory speed. Additionally, compared with the wild-type, reeler neurons displayed altered trajectories with greater deviation from a radial path. These results suggest that Reelin loss has early consequences for migration in the germinal zones that are portrayed as defective radial trajectories and migratory speeds. Together, these abnormalities can give rise to the increased cell dispersion observed in the reeler cortex.
Reelin 信号通路对于皮质的正常发育至关重要,但目前尚不清楚 Reelin 的功能主要是对皮质分层还是神经元迁移重要。有人提出,Reelin 可能只需要进行胞体转位,而不需要依赖神经胶质的运动。这意味着对 Reelin 作出反应的神经元的位置仅限于皮质板(CP)的外区。为了确定 Reelin 是否需要迁移到 CP 之外,我们使用延时成像来跟踪在生发区进行运动的细胞的行为。我们将重点放在脑室/室下区的迁移活动上,那里发生从双极到多极迁移的第一次转变,并且已知那里表达有功能性 Reelin 受体。尽管 Reelin 缺失,神经元在进行放射状迁移时没有困难,实际上显示出更快的迁移速度。此外,与野生型相比,reeler 神经元的轨迹发生改变,与放射状路径的偏差更大。这些结果表明,Reelin 的缺失对生发区的迁移有早期影响,表现为放射状轨迹和迁移速度的缺陷。这些异常共同导致了在 reeler 皮质中观察到的细胞分散增加。