Murine Embryonic Stem Cell-Derived Pyramidal Neurons Integrate into the Cerebral Cortex and Appropriately Project Axons to Subcortical Targets
Murine Embryonic Stem Cell-Derived Pyramidal Neurons Integrate into the Cerebral Cortex and Appropriately Project Axons to Subcortical Targets
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DOI：
10.1523/jneurosci.4318-09.2010
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发表时间：
2010-01-20
影响因子：
5.3
通讯作者：
Weimann, James M.
中科院分区：
文献类型：
--
作者：
Ideguchi, Makoto;Palmer, Theo D.;Weimann, James M.
虽然胚胎干细胞已被诱导分化为不同类型的神经细胞，但尚未发现具有正确形态和轴突连接的皮质投射神经元的产生。在这里，我们表明，在体外模式是关键的产生神经前体细胞(ES-NP)的能力，以形成皮质锥体神经元。在神经诱导的第一周，这些ES-NC开始表达前脑前体细胞特有的基因；另外一周的分化产生具有许多皮质锥体神经元特征的成熟神经元。在移植到小鼠大脑皮质后，这些特定的ES-NPC表现出正确的树突和轴突连接，以确定它们的区域位置。移植到运动皮质深层的ES-NPC分化为第5层锥体神经元，并将轴突延伸到远距离的皮质下目标，如桥脑和尾侧，直到锥体交叉和脊髓下行束，重要的是，不会将轴突延伸到不适当的目标，如上丘(SC)。移植到视皮质的ES-NPC将轴突延伸到SC和脑桥的背侧，但避开腹侧SC和锥体束，而移植到躯体感觉皮质深处的细胞则将轴突投射到腹侧SC，避开背侧SC。因此，这些数据表明，ES来源的皮质投射神经元可以整合到解剖学上相关的回路中。
Although embryonic stem (ES) cells have been induced to differentiate into diverse neuronal cell types, the production of cortical projection neurons with the correct morphology and axonal connectivity has not been demonstrated. Here, we show that in vitro patterning is critical for generating neural precursor cells (ES-NPCs) competent to form cortical pyramidal neurons. During the first week of neural induction, these ES-NPCs begin to express genes that are specific for forebrain progenitors; an additional week of differentiation produces mature neurons with many features of cortical pyramidal neurons. After transplantation into the murine cerebral cortex, these specified ES-NPCs manifest the correct dendritic and axonal connectivity for their areal location. ES-NPCs transplanted into the deep layers of the motor cortex differentiate into layer 5 pyramidal neurons and extend axons to distant subcortical targets such as the pons and as far caudal as the pyramidal decussation and descending spinal tract and, importantly, do not extend axons to inappropriate targets such as the superior colliculus (SC). ES-NPCs transplanted into the visual cortex extend axons to the dorsal aspect of the SC and pons but avoid ventral SC and the pyramidal tract, whereas cells transplanted deep into the somatosensory cortex project axons to the ventral SC, avoiding the dorsal SC. Thus, these data establish that ES-derived cortical projection neurons can integrate into anatomically relevant circuits.