An intrinsic mechanism of corticogenesis from embryonic stem cells
An intrinsic mechanism of corticogenesis from embryonic stem cells
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DOI：
10.1038/nature07287
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发表时间：
2008-09-18
期刊：
影响因子：
64.8
通讯作者：
Vanderhaeghen, Pierre
中科院分区：
文献类型：
--
作者：
Gaspard, Nicolas;Bouschet, Tristan;Vanderhaeghen, Pierre
大脑皮层通过数十个神经元亚型的协调生成而发育，但涉及的机制尚不清楚。在这里，我们展示了小鼠胚胎干细胞，在没有任何形态原的情况下培养，但在存在声波刺猬抑制剂的情况下，在体外概括了皮质发育的主要里程碑，导致了各种神经元的连续生成，这些神经元显示出真正皮质锥体神经元的最显著特征。当移植到大脑皮层时，这些神经元形成轴突投射模式，对应于广泛的皮质层，也对应于高度特定的皮质区，特别是视觉和边缘区域，从而表明皮质区的身份可以在不受大脑任何影响的情况下指定。内源性皮质生成的发现为神经元特化的机制提供了新的线索，并为脑疾病的建模和治疗开辟了新的途径。
The cerebral cortex develops through the coordinated generation of dozens of neuronal subtypes, but the mechanisms involved remain unclear. Here we show that mouse embryonic stem cells, cultured without any morphogen but in the presence of a sonic hedgehog inhibitor, recapitulate in vitro the major milestones of cortical development, leading to the sequential generation of a diverse repertoire of neurons that display most salient features of genuine cortical pyramidal neurons. When grafted into the cerebral cortex, these neurons develop patterns of axonal projections corresponding to a wide range of cortical layers, but also to highly specific cortical areas, in particular visual and limbic areas, thereby demonstrating that the identity of a cortical area can be specified without any influence from the brain. The discovery of intrinsic corticogenesis sheds new light on the mechanisms of neuronal specification, and opens new avenues for the modelling and treatment of brain diseases.