Sotelo C, Alvarado-Mallart R M, Frain M, Vernet M
INSERM U. 106, Hôpital de la Salpétrière, Paris, France.
J Neurosci. 1994 Jan;14(1):124-33. doi: 10.1523/JNEUROSCI.14-01-00124.1994.
Embryonic Purkinje cells (PCs) from cerebellar primordia grafted in adult pcd mutant cerebellum replace missing PCs of the host, and become synaptically integrated into the defective cerebellar circuit. This process of neuronal replacement starts with the invasion of grafted PCs into the host cerebellum, and their radial migration through its molecular layer. The present study is aimed at determining whether the glial axes for this migration are embryonic radial glial cells that comigrate with the grafted PCs, or adult Bergmann fibers of the host, transiently reexpressing the molecular cues needed for their guidance of the migration. Transplants from a transgenic mouse line (Krox-20/lacZ14) in which Bergmann fibers could be identified by lacZ expression reveal that, despite the presence of X-gal-stained Bergmann fibers in the graft remnants and of grafted PCs in the host molecular layer, all Bergmann fibers in the host cerebellum lack of beta-galactosidase activity. Thus, these migratory axes belong to the host, not to the donor. Transplants from normal isogenic mouse embryos show that during the radial migration of grafted PCs (7 d after grafting) the involved host Bergmann fibers reexpress nestin (identified with monoclonal antibody Rat-401 immunostaining), normally expressed only by immature Bergmann fibers. Five days later, when grafted PCs have arrested their migration, host Bergmann fibers again become Rat-401 negative. These results indicate that embryonic PCs can trigger in adult cerebellum the molecular changes necessary for their own migration and ultimate synaptic integration in the host cortical circuitry.
移植到成年pcd突变型小脑的小脑原基中的胚胎浦肯野细胞（PCs）替代了宿主缺失的PCs，并通过突触整合到有缺陷的小脑回路中。这种神经元替代过程始于移植的PCs侵入宿主小脑，并通过其分子层进行放射状迁移。本研究旨在确定这种迁移的神经胶质轴是与移植的PCs共同迁移的胚胎放射状胶质细胞，还是宿主的成年伯格曼纤维，后者短暂地重新表达引导迁移所需的分子线索。来自转基因小鼠品系（Krox-20/lacZ14）的移植实验表明，尽管移植残余物中有X-gal染色的伯格曼纤维，宿主分子层中有移植的PCs，但宿主小脑中所有伯格曼纤维均缺乏β-半乳糖苷酶活性。因此，这些迁移轴属于宿主，而非供体。来自正常同基因小鼠胚胎的移植实验显示，在移植的PCs进行放射状迁移期间（移植后7天），参与其中的宿主伯格曼纤维重新表达巢蛋白（用单克隆抗体Rat-401免疫染色鉴定），巢蛋白通常仅由未成熟的伯格曼纤维表达。五天后，当移植的PCs停止迁移时，宿主伯格曼纤维再次变为Rat-401阴性。这些结果表明，胚胎PCs能够在成年小脑中引发其自身迁移以及最终在宿主皮质回路中进行突触整合所需的分子变化。
