Götz M, Bolz J
Friedrich-Miescher-Labor, Max-Planck-Gesellschaft, Tübingen, Germany.
J Neurobiol. 1992 Sep;23(7):783-802. doi: 10.1002/neu.480230702.
During cortical development, neurons generated at the same time in the ventricular zone migrate out into the cortical plate and form a cortical layer (Berry and Eayrs, 1963, Nature 197:984-985; Berry and Rogers, 1965, J. Anat. 99:691-709). We have been studying both the formation and maintenance of cortical layers in slice cultures from rat cortex. The bromodeoxyuridine (BrdU) method was used to label cortical neurons on their birthday in vivo. When slice cultures were prepared from animals at different embryonic and postnatal ages, all cortical layers that have already been established in vivo remained preserved for several weeks in vitro. In slice cultures prepared during migration in the cortex, cells continued to migrate towards the pial side of the cortical slice, however, migration ceased after about 1 week in culture. Thus, cortical cells reached their final laminar position only in slice cultures from postnatal animals, whereas in embryonic slice, migrating cells became scattered throughout the cortex. Previous studies demonstrated that radial glia fibers are the major substrate for migrating neurons (Rakic, 1972, J. Comp. Neurol. 145:61-84; Hatten and Mason, 1990, Experientia 46:907-916). Using antibodies directed against the intermediate filament Vimentin, radial glial cells were detected in all slice cultures where cell migration did occur. Comparable to the glia development in vivo, radial glial fibers disappeared and astrocytes containing the glia fibrillary-associated protein (GFAP) differentiated in slice cultures from postnatal cortex, after the neurons have completed their migration. In contrast, radial glial cells were detected over the whole culture period, and very few astrocytes differentiated in embryonic slices, where cortical neurons failed to finish their migration. The results of this study indicate that the local environment is sufficient to sustain the layered organization of the cortex and support the migration of cortical neurons. In addition, our results reveal a close relationship between cell migration and the developmental status of glial cells.
在皮质发育过程中，在脑室区同时产生的神经元迁移到皮质板并形成一个皮质层（Berry和Eayrs，1963年，《自然》197:984 - 985；Berry和Rogers，1965年，《解剖学杂志》99:691 - 709）。我们一直在研究大鼠皮质切片培养物中皮质层的形成和维持。采用溴脱氧尿苷（BrdU）法在体内标记皮质神经元的生日。当从不同胚胎期和出生后年龄的动物制备切片培养物时，所有在体内已经形成的皮质层在体外可保存数周。在皮质迁移期制备的切片培养物中，细胞继续向皮质切片的软膜侧迁移，然而，培养约1周后迁移停止。因此，皮质细胞仅在出生后动物的切片培养物中到达其最终的层状位置，而在胚胎切片中，迁移的细胞散布于整个皮质。先前的研究表明，放射状胶质纤维是迁移神经元的主要基质（Rakic，1972年，《比较神经学杂志》145:61 - 84；Hatten和Mason，1990年，《实验》46:907 - 916）。使用针对中间丝波形蛋白的抗体，在所有发生细胞迁移的切片培养物中都检测到了放射状胶质细胞。与体内胶质细胞的发育类似，在神经元完成迁移后，放射状胶质纤维消失，含有胶质纤维酸性蛋白（GFAP）的星形胶质细胞在出生后皮质的切片培养物中分化。相反，在整个培养期都检测到放射状胶质细胞，而在胚胎切片中很少有星形胶质细胞分化，在胚胎切片中皮质神经元未能完成其迁移。本研究结果表明，局部环境足以维持皮质的分层组织并支持皮质神经元的迁移。此外，我们的结果揭示了细胞迁移与胶质细胞发育状态之间的密切关系。
