Migration pathways and fate determination of progenitors in the subventricular zone

哺乳动物前脑的绝大多数胶质细胞是在围产期由脑室下区（SVZ）的祖细胞生成的。我们用gfp逆转录病毒在体内标记新生（出生后0天，PO）大鼠前脑SVZ的祖细胞，并通过延时视频显微镜在P3切片上监测它们的运动，研究了祖细胞的迁移。我们发现了少量在胼胝体（CC）内切向迁移并越过中线的祖细胞。它们保持了相对统一的形态：前导突向对侧延伸，但没有分支或偏离迁移方向。净迁移需要前导过程的延长和核易位，CC中的迁移细胞表现出这两种模式。我们证实在P3 CC中存在无髓鞘的轴突束，但未能检测到任何径向定向的胶质突（静脉或glast免疫标记的纤维）跨越CC。共聚焦图像显示神经丝免疫标记的轴突与CC中表达gfp的祖细胞的主导过程非常接近。标记的纤维贯穿前皮层，到达左扣带区和运动区。检测逆转录病毒标记细胞在P28脑组织中的分布和最终命运。一小部分被标记的细胞在对侧半球被发现，作为少突胶质细胞和星形胶质细胞，它们主要分布在皮层和扣带区和次级运动区的底层白质上。这种分布模式似乎与胼胝体纤维的投射方向吻合得很好。因此，胶质祖细胞通过CC迁移，可能与无髓鞘轴突结合，在对侧半球定居。

The great majority of glial cells of the mammalian forebrain are generated in the perinatal period from progenitors in the subventricular zone(SVZ). We investigated the migration of progenitors from the neonatal(postnatal day O,PO) rat forebrain SVZ by labeling them in vivo with a GFP-retrovirus, and monitoring their movements by time-lapse video microscopy in P3 slices. We identified a small number of progenitors that migrated tangentially within the corpus callosum(CC) and crossed the midline. These retained a relatively uniform morphology : the leading process was extended toward the contralateral side, but showed no process branching or turning away from the migratory direction. Net migration requires the elongation of the leading process and nuclear translocation, and the migrating cells in the CC showed both modes. We confirmed the presence of unmyelihated axon bundles within the P3 CC, but failed to detect any radially directed glial processes(vimentin-or GLAST-immunolabeled fibers) spanning through the CC Confocal images showed a close proximity between neurofilament-immunolabeled axons and the leading process of the GFP-expressing progenitors in the CC. The destination of the callosal fibers was examined by applying Dil to the right cingulum ; the labeled fibers ran throughout the CC and reached the left cingulate and motor areas. The distribution and final fates of the retrovirus-labeled cells were examined in P28 brains. A small proportion of the labeled cells, were found in the contralateral hemisphere, where, as oligodendrocytes and astrocytes, they colonized predominantly the cortex and the underlying white matter of the cingulate and secondary motor areas. The distribution pattern appears to coincide well with the projection direction of the callosal fibers. Thus, glial progenitors migrate across the CC, presumably in conjunction with unmyelinated axons, to colonize the contralateral hemisphere.