Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany.
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, 03550 Sant Joan d'Alacant, Spain.
Cell. 2017 May 4;169(4):621-635.e16. doi: 10.1016/j.cell.2017.04.012.
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.
哺乳动物大脑皮层折叠成脑回和脑沟被认为是由基底祖细胞的扩增及其切线迁移所促进的。在这里，我们通过显示迁移过程中细胞间黏附的变化导致皮层折叠，为迁移在这个过程中的作用提供了一个分子机制。缺失 FLRT1 和 FLRT3 黏附分子的小鼠会出现具有保留分层结构和放射状胶质形态的宏观脑回。这些突变体中的皮层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，在没有 FLRT1/3 的情况下，由于细胞间黏附力降低、神经元迁移增加以及皮质板中的聚类，导致了脑沟的形成。值得注意的是，FLRT1/3 在人类大脑皮层和雪貂未来的脑沟区域中的表达水平较低，这表明细胞间黏附是跨物种皮层折叠的关键调节因子。
