During development, two coordinated events shape the morphology of the mammalian cerebral cortex, leading to the cortex’s columnar and layered structure: the proliferation of neuronal progenitors and cortical migration. Pyramidal neurons originating from germinal zones migrate along radial glial fibers to their final position in the cortical plate by both radial migration and tangential dispersion. These processes rely on the delicate balance of intercellular adhesive and repulsive signaling that takes place between neurons interacting with different substrates and guidance cues. Here, we focus on the function of the cell adhesion molecules fibronectin leucine-rich repeat transmembrane proteins (FLRTs) in regulating both the radial migration of neurons, as well as their tangential spread, and the impact these processes have on cortex morphogenesis. In combining structural and functional analysis, recent studies have begun to reveal how FLRT-mediated responses are precisely tuned – from forming different protein complexes to modulate either cell adhesion or repulsion in neurons. These approaches provide a deeper understanding of the context-dependent interactions of FLRTs with multiple receptors involved in axon guidance and synapse formation that contribute to finely regulated neuronal migration.

在发育过程中，两个相互协调的事件塑造了哺乳动物大脑皮层的形态，导致了皮层的柱状和分层结构：神经元祖细胞的增殖和皮层迁移。起源于生发区的金字塔形神经元通过径向迁移和切向弥散沿着径向神经胶质纤维迁移到它们在皮质板中的最终位置。这些过程依赖于细胞间黏附和排斥信号之间的微妙平衡，这发生在与不同底物和引导线索相互作用的神经元之间。在这里，我们专注于细胞粘附分子富含纤连蛋白亮氨酸的重复跨膜蛋白（FLRTs）在调节神经元的径向迁移及其切向扩散以及这些过程对皮层形态发生的影响中的功能。通过结合结构和功能分析，最近的研究开始揭示如何精确调节FLRT介导的反应-从形成不同的蛋白质复合物来调节神经元的细胞粘附或排斥。这些方法提供了更深入的了解FLRTs与轴突引导和突触形成中涉及的多种受体的上下文相关的相互作用，这些受体有助于精细调节的神经元迁移。