Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum.

Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum.
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DOI:
10.1186/1749-8104-5-23
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发表时间:
2010-09-01
期刊:
影响因子:
3.6
通讯作者:
Ogawa M
Ogawa M
中科院分区:
生物学3区
文献类型:
--
作者:
Miyata T;Ono Y;Okamoto M;Masaoka M;Sakakibara A;Kawaguchi A;Hashimoto M;Ogawa M

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小脑皮质发生开始于小鼠胚胎第14.5天(E14.5)时浦肯野细胞组装到浦肯野板(PP)中。虽然PP形成对分泌蛋白Reelin的依赖性是众所周知的,并且流行的模型表明浦肯野细胞沿连接心室和软脑膜表面的“放射状胶质”纤维沿着迁移,但尚不清楚浦肯野细胞如何响应Reelin启动PP。此外,尚不清楚新生的浦肯野细胞在体内的样子。浦肯野细胞何时以及如何开始轴突发生也必须阐明。我们发现,浦肯野细胞产生E10.5在后室周区域的外侧小脑切向迁移后,只有短暂的径向迁移,朝向前方,表现出细长的形态与轴突在E12.5一致。在E13.5它们的胞体到达外部/背侧区域后,它们通过非轴突(树突样)过程的重塑和朝向表面的Reelin丰富区的体运动的之字形模式改变E14.5的“姿势”,而它们的轴突样纤维保持相对较深,这将胞体包装部分划分为板。在reeler小脑,早期出生的后外侧浦肯野细胞最初是正常的迁移过程中向前延伸的轴突样纤维,直到E13.5,但随后未能形成PP由于缺乏姿势改变的步骤。先前未知的行为揭示了一个子集的浦肯野细胞早期出生在小脑后外侧:切线迁移;早期轴突生成;和Reelin依赖的重定向启动PP的形成。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个脑形态发生。
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.
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