Inside-Out Radial Migration Facilitates Lineage-Dependent Neocortical Microcircuit Assembly.

Inside-Out Radial Migration Facilitates Lineage-Dependent Neocortical Microcircuit Assembly.
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DOI:
10.1016/j.neuron.2015.05.002
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发表时间:
2015-06-03
期刊:
影响因子:
16.2
通讯作者:
Shi SH
Shi SH
中科院分区:
医学1区
文献类型:
--
作者:
He S;Li Z;Ge S;Yu YC;Shi SH

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新皮层兴奋性神经元以出生日期依赖的由内向外的方式沿放射状胶质祖细胞(RGP)的胶质纤维沿着放射状迁移。然而,这种公认的有序神经元迁移的确切功能意义在很大程度上仍然不清楚。在这里,我们表明,强的电突触选择性地形成RGP和他们的新生儿后代之间,在胚胎阶段的个体发育放射状克隆的姐妹兴奋性神经元之间。有趣的是,姐妹兴奋性神经元之间的优先电耦合,但不是RGP和新生儿后代之间的,在缺乏REELIN的小鼠或DISABLED-1的克隆耗竭后被消除,这损害了发育中的新皮层中由内而外的放射状神经元迁移模式。此外,横向分散姐妹兴奋性神经元的Ephrin-A配体或受体的水平增加也破坏径向对齐的姐妹兴奋性神经元之间的优先电耦合。这些结果表明,RGP引导的由内向外的径向神经元迁移有利于在新皮层中的谱系依赖的精确的柱状微电路的初始组装。
Neocortical excitatory neurons migrate radially along the glial fibers of mother radial glial progenitors (RGPs) in a birth date-dependent inside-out manner. However, the precise functional significance of this well-established orderly neuronal migration remains largely unclear. Here, we show that strong electrical synapses selectively form between RGPs and their newborn progeny, and between sister excitatory neurons in ontogenetic radial clones at the embryonic stage. Interestingly, the preferential electrical coupling between sister excitatory neurons, but not that between RGP and newborn progeny, is eliminated in mice lacking REELIN or upon clonal depletion of DISABLED-1, which compromises the inside-out radial neuronal migration pattern in the developing neocortex. Moreover, increased levels of Ephrin-A ligand or receptor that laterally disperse sister excitatory neurons also disrupt preferential electrical coupling between radially aligned sister excitatory neurons. These results suggest that RGP-guided inside-out radial neuronal migration facilitates the initial assembly of lineage-dependent precise columnar microcircuits in the neocortex.