Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Neural Dev. 2010 Sep 1;5:23. doi: 10.1186/1749-8104-5-23.
Cerebellar corticogenesis begins with the assembly of Purkinje cells into the Purkinje plate (PP) by embryonic day 14.5 (E14.5) in mice. Although the dependence of PP formation on the secreted protein Reelin is well known and a prevailing model suggests that Purkinje cells migrate along the 'radial glial' fibers connecting the ventricular and pial surfaces, it is not clear how Purkinje cells behave in response to Reelin to initiate the PP. Furthermore, it is not known what nascent Purkinje cells look like in vivo. When and how Purkinje cells start axonogenesis must also be elucidated.
We show that Purkinje cells generated on E10.5 in the posterior periventricular region of the lateral cerebellum migrate tangentially, after only transiently migrating radially, towards the anterior, exhibiting an elongated morphology consistent with axonogenesis at E12.5. After their somata reach the outer/dorsal region by E13.5, they change 'posture' by E14.5 through remodeling of non-axon (dendrite-like) processes and a switchback-like mode of somal movement towards a superficial Reelin-rich zone, while their axon-like fibers remain relatively deep, which demarcates the somata-packed portion as a plate. In reeler cerebella, the early born posterior lateral Purkinje cells are initially normal during migration with anteriorly extended axon-like fibers until E13.5, but then fail to form the PP due to lack of the posture-change step.
Previously unknown behaviors are revealed for a subset of Purkinje cells born early in the posteior lateral cerebellum: tangential migration; early axonogenesis; and Reelin-dependent reorientation initiating PP formation. This study provides a solid basis for further elucidation of Reelin's function and the mechanisms underlying the cerebellar corticogenesis, and will contribute to the understanding of how polarization of individual cells drives overall brain morphogenesis.
小脑皮质发生始于胚胎第 14.5 天（E14.5）时浦肯野细胞在浦肯野板（PP）中的组装。尽管众所周知，PP 的形成依赖于分泌蛋白 Reelin，并且流行的模型表明浦肯野细胞沿着连接脑室和软脑膜表面的“放射状胶质”纤维迁移，但尚不清楚浦肯野细胞如何对 Reelin 做出反应以启动 PP。此外，尚不清楚体内新生的浦肯野细胞是什么样子。浦肯野细胞何时以及如何开始轴突发生也必须阐明。
我们表明，E10.5 在外侧小脑后室旁区产生的浦肯野细胞在短暂地沿放射状迁移后，沿切线方向迁移，在 E12.5 时表现出与轴突发生一致的伸长形态。E13.5 时，它们的体到达外/背区后，E14.5 通过非轴突（树突样）过程的重塑和躯体的折返样运动模式，改变“姿势”，朝向富含 Reelin 的浅层区域，而它们的轴突样纤维仍保持相对较深，这将体部密集的部分划定为板。在 reeler 小脑中，早期出生的后外侧浦肯野细胞在迁移过程中最初是正常的，具有向前延伸的轴突样纤维，直到 E13.5，但随后由于缺乏姿势变化步骤而无法形成 PP。
揭示了早期在后外侧小脑中产生的浦肯野细胞亚群的未知行为：切线迁移；早期轴突发生；以及 Reelin 依赖性重定向启动 PP 形成。这项研究为进一步阐明 Reelin 的功能和小脑皮质发生的机制提供了坚实的基础，并将有助于理解单个细胞的极化如何驱动整体大脑形态发生。
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