Gaspard Nicolas, Bouschet Tristan, Hourez Raphael, Dimidschstein Jordane, Naeije Gilles, van den Ameele Jelle, Espuny-Camacho Ira, Herpoel Adèle, Passante Lara, Schiffmann Serge N, Gaillard Afsaneh, Vanderhaeghen Pierre
IRIBHM (Institute for Interdisciplinary Research), Université Libre de Bruxelles (ULB).
Nature. 2008 Sep 18;455(7211):351-7. doi: 10.1038/nature07287. Epub 2008 Aug 17.
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.
大脑皮层通过数十种神经元亚型的协同生成而发育，但其中涉及的机制仍不清楚。在这里，我们表明，小鼠胚胎干细胞在没有任何形态发生素的情况下培养，但在存在音猬因子抑制剂的情况下，在体外重现了皮层发育的主要里程碑，导致依次产生各种神经元，这些神经元表现出真正皮层锥体神经元的最显著特征。当移植到大脑皮层时，这些神经元形成的轴突投射模式对应于广泛的皮层层，也对应于高度特定的皮层区域，特别是视觉和边缘区域，从而证明皮层区域的身份可以在没有大脑任何影响的情况下被确定。内在皮质发生的发现为神经元特化机制提供了新的线索，并为脑部疾病的建模和治疗开辟了新途径。
