Progressive restriction in fate potential by neural progenitors during cerebral cortical development.
Progressive restriction in fate potential by neural progenitors during cerebral cortical development.
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发表时间：
2000-07
期刊：
影响因子：
4.6
通讯作者：
Aparna Desai;S. Mcconnell
中科院分区：
文献类型：
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作者：
Aparna Desai;S. Mcconnell
在大脑皮质发育的早期阶段，脑室区域的前体细胞是多能的，在连续的细胞分裂中产生多层神经元。它们后代的层状命运取决于细胞在有丝分裂之前对哪些环境信号做出反应。然而，在神经发生结束时，祖细胞线性地致力于产生上层神经元。在这里，我们评估了处于皮质发育中期的祖细胞的层状命运潜力。第四层神经元的祖细胞首先被移植到正在产生第二/3层的较老的大脑中。移植的神经元采用了适合新环境的层状命运(第2/3层)，揭示了第4层前体细胞具有多能性。然后，将中期祖细胞移植到更年轻的环境中，在这个环境中，第六层神经元正在生成。移植的神经元绕过了第六层，揭示了第四层的祖细胞具有受限的命运潜力，不能对触发第六层产生的环境线索做出反应。相反，移植的细胞迁移到第四层，这是它们起源的典型位置，也迁移到第五层，一个既不适合宿主也不适合供体环境的位置。由于第5层神经发生在祖细胞被移出进行移植的阶段已经完成，因此对层状命运潜力的限制必须滞后于皮质层的最终产生。这些结果表明，内在和环境因素的组合控制着皮质前体细胞产生不同层次神经元的能力。
During early stages of cerebral cortical development, progenitor cells in the ventricular zone are multipotent, producing neurons of many layers over successive cell divisions. The laminar fate of their progeny depends on environmental cues to which the cells respond prior to mitosis. By the end of neurogenesis, however, progenitors are lineally committed to producing upper-layer neurons. Here we assess the laminar fate potential of progenitors at a middle stage of cortical development. The progenitors of layer 4 neurons were first transplanted into older brains in which layer 2/3 was being generated. The transplanted neurons adopted a laminar fate appropriate for the new environment (layer 2/3), revealing that layer 4 progenitors are multipotent. Mid-stage progenitors were then transplanted into a younger environment, in which layer 6 neurons were being generated. The transplanted neurons bypassed layer 6, revealing that layer 4 progenitors have a restricted fate potential and are incompetent to respond to environmental cues that trigger layer 6 production. Instead, the transplanted cells migrated to layer 4, the position typical of their origin, and also to layer 5, a position appropriate for neither the host nor the donor environment. Because layer 5 neurogenesis is complete by the stage that progenitors were removed for transplantation, restrictions in laminar fate potential must lag behind the final production of a cortical layer. These results suggest that a combination of intrinsic and environmental cues controls the competence of cortical progenitor cells to produce neurons of different layers.