Ephrin-B1 Controls the Columnar Distribution of Cortical Pyramidal Neurons by Restricting Their Tangential Migration
Ephrin-B1 Controls the Columnar Distribution of Cortical Pyramidal Neurons by Restricting Their Tangential Migration
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DOI：
10.1016/j.neuron.2013.07.015
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发表时间：
2013-09-18
期刊：
影响因子：
16.2
通讯作者：
Vanderhaeghen, Pierre
中科院分区：
文献类型：
--
作者：
Dimidschstein, Jordane;Passante, Lara;Vanderhaeghen, Pierre
大脑皮层的神经元是以层和柱的形式组织的。与层流模式不同，柱状组织的潜在机制在很大程度上仍未被探索。在这里，我们通过控制锥体神经元的非径向迁移步骤，证明了ePhrin-B1在这一过程中发挥了关键作用。在体内，ePhin-B1的功能增强导致锥体神经元的切向运动减少，导致异常的神经元聚集。相反，在ePhin-B1基因中断后，皮质神经元表现出更广泛的侧向分散，导致个体发育柱扩大。动态分析显示，在多极期，ePhrin-B1通过限制轴突的伸展和切向迁移来控制锥体神经元的侧向扩散。此外，我们确定了P-REx1，一种鸟嘌呤交换因子，是在多极阶段控制迁移所必需的下游ePhin-B1效应器。我们的结果表明，ewitin-B1抑制锥体神经元的非径向迁移，从而控制皮质柱的模式。
Neurons of the cerebral cortex are organized in layers and columns. Unlike laminar patterning, the mechanisms underlying columnar organization remain largely unexplored. Here, we show that ephrin-B1 plays a key role in this process through the control of nonradial steps of migration of pyramidal neurons. In vivo gain of function of ephrin-B1 resulted in a reduction of tangential motility of pyramidal neurons, leading to abnormal neuronal clustering. Conversely, following genetic disruption of ephrin-B1, cortical neurons displayed a wider lateral dispersion, resulting in enlarged ontogenic columns. Dynamic analyses revealed that ephrin-B1 controls the lateral spread of pyramidal neurons by limiting neurite extension and tangential migration during the multipolar phase. Furthermore, we identified P-Rex1, a guanine-exchange factor for Rac3, as a downstream ephrin-B1 effector required to control migration during the multipolar phase. Our results demonstrate that ephrin-B1 inhibits nonradial migration of pyramidal neurons, thereby controlling the pattern of cortical columns.