Migration pathways and fate determination of progenitors in the subventricular zone

室下区祖细胞的迁移途径和命运决定

• 批准号: 14580767
• 负责人: KAKITA Akiyoshi
• 金额: $ 1.98万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580767/
• 关键词: Glial progenitor; Neuronal progenitor; Fate determination; Retrovirus; Fluorescent molecule; Migratory behavior; Brain stem cells; Subventricular zone

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.

哺乳动物前脑的绝大多数胶质细胞是在围产期由室管膜下区（SVZ）的祖细胞产生的。我们研究了从新生儿（出生后第O天，PO）大鼠前脑SVZ的祖细胞的迁移标记他们在体内与GFP-逆转录病毒，并监测他们的运动延时视频显微镜在P3切片。我们确定了少量的祖细胞，迁移切向胼胝体（CC）内，并越过中线。这些保留了一个相对统一的形态：领先的过程是向对侧延伸，但没有显示出过程分支或转向远离迁移方向。细胞的净迁移需要前导过程的延长和核转位，而CC中的迁移细胞同时具有这两种方式。我们证实了存在的unmyelihated轴突束内的P3 CC，但未能检测到任何放射状定向的胶质细胞过程（波形蛋白或GLAST免疫标记的纤维）跨越CC共聚焦图像显示神经元免疫标记的轴突之间的密切接近和领先的过程中的GFP表达的祖细胞的CC。通过将Dil应用于右侧扣带来检查胼胝体纤维的目的地;标记的纤维贯穿CC并到达左侧扣带和运动区。在P28脑中检查逆转录病毒标记细胞的分布和最终命运。在对侧半球发现了一小部分标记细胞，在那里，作为少突胶质细胞和星形胶质细胞，它们主要定植在皮质和扣带和次级运动区的下层白色物质。其分布与胼胝体纤维的投射方向一致。因此，神经胶质祖细胞迁移通过CC，可能与无髓鞘轴突一起，定居在对侧半球。

项目成果

Kakita A Inenaga C, Sakamoto M, Takahashi H.: "Neuroanl migration disturbance and consequent cytoarchitecture in the cerebral cortex following transplacental administration of methylmercury"Acta Neuropathol. 104. 409-417 (2002)

Kakita A Inenaga C、Sakamoto M、Takahashi H.：“经胎盘施用甲基汞后大脑皮层的神经迁移紊乱和随之而来的细胞结构”Acta Neuropathol。

Kakita A, Zerlin M, Takahashi H, Goldman JE.: "Some glial progenitors in the neonatal subventricular zone mi grate through the corpus callosum to the contralateral cerebral hemisphere."J Comp Neurol. 458. 381-388 (2003)

Kakita A、Zerlin M、Takahashi H、Goldman JE.：“新生儿室下区的一些神经胶质祖细胞通过胼胝体迁移到对侧大脑半球。”J Comp Neurol。

Akiyoshi Kakita, et al.: "Neuronal migration disturbance and consequent cytoarchitecture in the cerebral cortex following transplacental administration of methylmercury"Acta Neuropathol. 104(4). 409-417 (2002)

Akiyoshi Kakita 等人：“经胎盘施用甲基汞后大脑皮层中的神经元迁移紊乱和随后的细胞结构”Acta Neuropathol。

Akiyoshi Kakita, et al.: "Bilateral periventricular nodular heterotopia due to filamin l gene mutation : widespread glomeruloid microvascular anomaly and dysplastic cytoarchitecture in the cerebral cortex"Acta Neuropathol. 104(6). 649-657 (2002)

Akiyoshi Kakita 等人：“Filamin l 基因突变引起的双侧脑室周围结节性异位：大脑皮质中广泛的肾小球微血管异常和发育不良的细胞结构”Acta Neuropathol。

Akiyoshi Kakita, et al.: "Some glial progenitors migrate through the corpus callosum to the contralateral cerebral hemisphere"J Comp Neurol. (in press).

Akiyoshi Kakita 等人：“一些神经胶质祖细胞通过胼胝体迁移到对侧大脑半球”J Comp Neurol。