Hansen Andi H, Hippenmeyer Simon
Institute of Science and Technology Austria, Klosterneuburg, Austria.
Front Cell Dev Biol. 2020 Sep 25;8:574382. doi: 10.3389/fcell.2020.574382. eCollection 2020.
Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final target lamina, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating the specific sequential steps of radial neuronal migration are however still unclear, let alone the effects and interactions with the extracellular environment. In any context, cells will always be exposed to a complex extracellular environment consisting of (1) secreted factors acting as potential signaling cues, (2) the extracellular matrix, and (3) other cells providing cell-cell interaction through receptors and/or direct physical stimuli. Most studies so far have described and focused mainly on intrinsic cell-autonomous gene functions in neuronal migration but there is accumulating evidence that non-cell-autonomous-, local-, systemic-, and/or whole tissue-wide effects substantially contribute to the regulation of radial neuronal migration. These non-cell-autonomous effects may differentially affect cortical neuron migration in distinct cellular environments. However, the cellular and molecular natures of such non-cell-autonomous mechanisms are mostly unknown. Furthermore, physical forces due to collective migration and/or community effects (i.e., interactions with surrounding cells) may play important roles in neocortical projection neuron migration. In this concise review, we first outline distinct models of non-cell-autonomous interactions of cortical projection neurons along their radial migration trajectory during development. We then summarize experimental assays and platforms that can be utilized to visualize and potentially probe non-cell-autonomous mechanisms. Lastly, we define key questions to address in the future.
新生皮质投射神经元从其出生地向最终目标层的协同径向迁移，是大脑皮质组装的关键步骤。然而，调节径向神经元迁移特定连续步骤的细胞和分子机制仍不清楚，更不用说其与细胞外环境的作用和相互作用了。在任何情况下，细胞总是会暴露于一个复杂的细胞外环境中，该环境由以下部分组成：（1）作为潜在信号线索的分泌因子，（2）细胞外基质，以及（3）通过受体和/或直接物理刺激提供细胞间相互作用的其他细胞。到目前为止，大多数研究主要描述并聚焦于神经元迁移中内在的细胞自主基因功能，但越来越多的证据表明，非细胞自主、局部、全身和/或整个组织范围的效应在很大程度上有助于调节径向神经元迁移。这些非细胞自主效应可能在不同的细胞环境中对皮质神经元迁移产生不同的影响。然而，这种非细胞自主机制的细胞和分子本质大多未知。此外，集体迁移和/或群落效应（即与周围细胞的相互作用）产生的物理力可能在新皮质投射神经元迁移中发挥重要作用。在这篇简要综述中，我们首先概述了发育过程中皮质投射神经元沿其径向迁移轨迹的非细胞自主相互作用的不同模型。然后，我们总结了可用于可视化并可能探究非细胞自主机制的实验分析方法和平台。最后，我们确定了未来需要解决的关键问题。
