Enhanced Axonal Extension of Subcortical Projection Neurons Isolated from Murine Embryonic Cortex using Neuropilin-1.
Enhanced Axonal Extension of Subcortical Projection Neurons Isolated from Murine Embryonic Cortex using Neuropilin-1.
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DOI：
10.3389/fncel.2017.00123
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发表时间：
2017
影响因子：
5.3
通讯作者：
Takahashi J
中科院分区：
文献类型：
--
作者：
Sano N;Shimogawa T;Sakaguchi H;Ioroi Y;Miyawaki Y;Morizane A;Miyamoto S;Takahashi J
小鼠胚胎的大脑皮层组织和多能干细胞（PSC）源性神经元可以在大脑中存活并将轴突延伸到脊髓。为了在移植后有效地将细胞整合到皮质脊髓束（CST），皮质运动神经元的诱导或选择是重要的。然而，关于合适的细胞群的精确信息仍然不清楚。为了解决这个问题，我们分离细胞表达神经纤毛蛋白-1（NRP 1），一个主要的轴突导向分子受体在早期发育阶段，从E14.5小鼠胚胎额叶皮层荧光激活细胞分选。NRP 1+细胞的聚集体在体外逐渐表达皮质下投射神经元标记物Ctip 2和VGluT 1以及轴突导向分子受体Robo 1和在结直肠钙质瘤（Dcc）中缺失，表明它们含有早期皮质下投射神经元。我们将NRP 1+细胞移植到P2新生小鼠的额叶皮质中。与来源于NRP 1-或未分选细胞的移植物相比，来源于NRP 1+细胞的移植物沿着沿着CST向脊髓延伸了更多的轴突。我们的数据表明，从胚胎大脑皮质中分选NRP 1+细胞可以丰富皮质下投射神经元，从而重建CST。
The cerebral cortical tissue of murine embryo and pluripotent stem cell (PSC)-derived neurons can survive in the brain and extend axons to the spinal cord. For efficient cell integration to the corticospinal tract (CST) after transplantation, the induction or selection of cortical motor neurons is important. However, precise information about the appropriate cell population remains unclear. To address this issue, we isolated cells expressing Neuropilin-1 (NRP1), a major axon guidance molecule receptor during the early developmental stage, from E14.5 mouse embryonic frontal cortex by fluorescence-activated cell sorting. Aggregates of NRP1+ cells gradually expressed subcortical projection neuron markers, Ctip2 and VGluT1, and axon guidance molecule receptors, Robo1 and deleted in colorectal calcinoma (Dcc), in vitro, suggesting that they contained early-stage subcortical projection neurons. We transplanted NRP1+ cells into the frontal cortex of P2 neonatal mice. Compared with grafts derived from NRP1− or unsorted cells, those derived from NRP1+ cells extended a larger number of axons to the spinal cord along the CST. Our data suggest that sorting NRP1+ cells from the embryonic cerebral cortex enriches subcortical projection neurons to reconstruct the CST.