Department of Neuroscience, Yale University, New Haven, CT 06520, USA.
Department of Neuroscience, Yale University, New Haven, CT 06520, USA.; Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Sci Adv. 2016 Feb 26;2(2):e1501733. doi: 10.1126/sciadv.1501733. eCollection 2016 Feb.
Cortical columns are basic cellular and functional units of the cerebral cortex that are malformed in many brain disorders, but how they initially develop is not well understood. Using an optogenetic sensor in the mouse embryonic forebrain, we demonstrate that Ca(2+) fluxes propagate bidirectionally within the elongated fibers of radial glial cells (RGCs), providing a novel communication mechanism linking the proliferative and postmitotic zones before the onset of synaptogenesis. Our results indicate that Ca(2+) activity along RGC fibers provides feedback information along the radial migratory pathway, influencing neurogenesis and migration during early column development. Furthermore, we find that this columnar Ca(2+) propagation is induced by Notch and fibroblast growth factor activities classically implicated in cortical expansion and patterning. Thus, cortical morphogens and growth factors may influence cortical column assembly in part by regulating long-distance Ca(2+) communication along the radial axis of cortical development.
皮质柱是大脑皮层的基本细胞和功能单位，在许多脑部疾病中都存在畸形，但它们最初是如何发育的还不是很清楚。我们使用小鼠胚胎前脑中的光遗传传感器，证明了 Ca(2+) 流在放射状胶质细胞 (RGC) 的长纤维中双向传播，为突触发生前连接增殖区和有丝分裂后区提供了一种新的通讯机制。我们的结果表明，RGC 纤维上的 Ca(2+) 活性沿着放射状迁移途径提供反馈信息，影响早期柱发育过程中的神经发生和迁移。此外，我们发现这种柱状 Ca(2+) 传播是由 Notch 和成纤维细胞生长因子活性诱导的，这两种因子经典地参与了皮质扩张和模式形成。因此，皮质形态发生素和生长因子可能通过调节皮质发育的放射轴上的远距离 Ca(2+) 通讯，在一定程度上影响皮质柱的组装。
