Trajectory Analysis Unveils Reelin's Role in the Directed Migration of Granule Cells in the Dentate Gyrus

作者：Shaobo Wang, Bianka Brunne, Shanting Zhao, Xuejun Chai, Jiawei Li, Jeremie Lau, Antonio Virgilio Failla, Bernd Zobiak, Mirjam Sibbe, Gary L. Westbrook, David Lutz, Michael Frotscher · 发表于：Journal of Neuroscience · 年份：2017 · DOI：10.1523/jneurosci.0988-17.2017 · 被引用次数：30 · 研究领域：Neurogenesis and neuroplasticity mechanisms、Axon Guidance and Neuronal Signaling、Nerve injury and regeneration

Reelin controls neuronal migration and layer formation. Previous studies in reeler mice deficient in Reelin focused on the result of the developmental process in fixed tissue sections. It has remained unclear whether Reelin affects the migratory process, migration directionality, or migrating neurons guided by the radial glial scaffold. Moreover, Reelin has been regarded as an attractive signal because newly generated neurons migrate toward the Reelin-containing marginal zone. Conversely, Reelin might be a stop signal because migrating neurons in reeler , but not in wild-type mice, invade the marginal zone. Here, we monitored the migration of newly generated proopiomelanocortin-EGFP -expressing dentate granule cells in slice cultures from reeler , reeler -like mutants and wild-type mice of either sex using real-time microscopy. We discovered that not the actual migratory process and migratory speed, but migration directionality of the granule cells is controlled by Reelin. While wild-type granule cells migrated toward the marginal zone of the dentate gyrus, neurons in cultures from reeler and reeler -like mutants migrated randomly in all directions as revealed by vector analyses of migratory trajectories. Moreover, live imaging of granule cells in reeler slices cocultured to wild-type dentate gyrus showed that the reeler neurons changed their directions and migrated toward the Reelin-containing marginal zone of the wild-type culture, thus forming a compact granule cell layer....