Regulation of Cerebral Cortex Folding by Controlling Neuronal Migration via FLRT Adhesion Molecules
Regulation of Cerebral Cortex Folding by Controlling Neuronal Migration via FLRT Adhesion Molecules
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DOI：
10.1016/j.cell.2017.04.012
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发表时间：
2017-05-04
期刊：
影响因子：
64.5
通讯作者：
Klein, Ruediger
中科院分区：
文献类型：
--
作者：
del Toro, Daniel;Ruff, Tobias;Klein, Ruediger
哺乳动物大脑皮层折叠成沟回被认为是由基底祖细胞的扩增和它们的切向迁移所促进的。在这里，我们提供了一个分子机制的迁移在这一过程中的作用，表明迁移皮层神经元的细胞间粘附的变化导致皮质折叠。FLRT 1和FLRT 3粘附分子缺失的小鼠出现保留分层组织和放射状胶质形态的宏观脑沟。这些突变体的皮质折叠不需要祖细胞扩增，但依赖于神经元迁移的变化。分析和模拟表明，在FLRT 1/3的情况下，脑沟的形成是由于细胞间粘附减少，神经元迁移增加和皮质板中的聚集。值得注意的是，FLRT 1/3在人类皮层和未来雪貂的沟区表达较低，表明细胞间粘附是跨物种皮层折叠的关键调节因子。
The folding of the mammalian cerebral cortex into sulci and gyri is thought to be favored by the amplification of basal progenitor cells and their tangential migration. Here, we provide a molecular mechanism for the role of migration in this process by showing that changes in intercellular adhesion of migrating cortical neurons result in cortical folding. Mice with deletions of FLRT1 and FLRT3 adhesion molecules develop macroscopic sulci with preserved layered organization and radial glial morphology. Cortex folding in these mutants does not require progenitor cell amplification but is dependent on changes in neuron migration. Analyses and simulations suggest that sulcus formation in the absence of FLRT1/3 results from reduced intercellular adhesion, increased neuron migration, and clustering in the cortical plate. Notably, FLRT1/3 expression is low in the human cortex and in future sulcus areas of ferrets, suggesting that intercellular adhesion is a key regulator of cortical folding across species.