Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Center for Studies in Physics and Biology and Kavli Neural Systems Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Cell Stem Cell. 2018 Jul 5;23(1):60-73.e6. doi: 10.1016/j.stem.2018.05.024. Epub 2018 Jun 21.
Cortical deep projection neurons (DPNs) are implicated in neurodevelopmental disorders. Although recent findings emphasize post-mitotic programs in projection neuron fate selection, the establishment of primate DPN identity during layer formation is not well understood. The subplate lies underneath the developing cortex and is a post-mitotic compartment that is transiently and disproportionately enlarged in primates in the second trimester. The evolutionary significance of subplate expansion, the molecular identity of its neurons, and its contribution to primate corticogenesis remain open questions. By modeling subplate formation with human pluripotent stem cells (hPSCs), we show that all classes of cortical DPNs can be specified from subplate neurons (SPNs). Post-mitotic WNT signaling regulates DPN class selection, and DPNs in the caudal fetal cortex appear to exclusively derive from SPNs. Our findings indicate that SPNs have evolved in primates as an important source of DPNs that contribute to cortical lamination prior to their known role in circuit formation.
皮质深投射神经元（DPNs）与神经发育障碍有关。尽管最近的研究结果强调了在投射神经元命运选择中存在有丝分裂后程序，但在层形成过程中灵长类动物 DPN 特征的确立仍未得到很好的理解。基板位于发育中的皮质下方，是一个有丝分裂后细胞区室，在灵长类动物的第二个三个月期间暂时不成比例地扩大。基板扩张的进化意义、其神经元的分子特征以及对灵长类皮质发生的贡献仍然是悬而未决的问题。通过用人多能干细胞（hPSCs）模拟基板形成，我们表明所有类型的皮质 DPN 都可以从基板神经元（SPNs）中指定。有丝分裂后 WNT 信号调节 DPN 类别的选择，并且尾侧胎儿皮质中的 DPN 似乎仅源自 SPN。我们的研究结果表明，在灵长类动物中，SPN 已经进化为 DPN 的重要来源，它们在已知的回路形成作用之前就有助于皮质分层。
