Department of Cell and Developmental Biology, University College London, London, UK.
Institute of Ophthalmology, University College London, London, UK.
Cereb Cortex. 2018 Jul 1;28(7):2577-2593. doi: 10.1093/cercor/bhy082.
Vascular endothelial growth factor (Vegfa) is essential for promoting the vascularization of the embryonic murine forebrain. In addition, it directly influences neural development, although its role in the forming forebrain is less well elucidated. It was recently suggested that Vegfa may influence the development of GABAergic interneurons, inhibitory cells with crucial signaling roles in cortical neuronal circuits. However, the mechanism by which it affects interneuron development remains unknown. Here we investigated the developmental processes by which Vegfa may influence cortical interneuron development by analyzing transgenic mice that ubiquitously express the Vegfa120 isoform to perturb its signaling gradient. We found that interneurons reach the dorsal cortex at mid phases of corticogenesis despite an aberrant vascular network. Instead, endothelial ablation of Vegfa alters cortical interneuron numbers, their intracortical distribution and spatial proximity to blood vessels. We show for the first time that vascular-secreted guidance factors promote early-migrating interneurons in the intact forebrain in vivo and identify a novel role for vascular-Vegfa in this process.
血管内皮生长因子（Vegfa）对于促进胚胎鼠前脑的血管生成至关重要。此外，它还直接影响神经发育，尽管其在前脑形成中的作用还不太清楚。最近有人提出，Vegfa 可能影响 GABA 能中间神经元的发育，GABA 能中间神经元是皮质神经元回路中具有关键信号作用的抑制性细胞。然而，它影响中间神经元发育的机制尚不清楚。在这里，我们通过分析广泛表达 Vegfa120 同工型的转基因小鼠来研究 Vegfa 可能影响皮质中间神经元发育的发育过程，从而扰乱其信号梯度。我们发现，尽管血管网络异常，但中间神经元在皮质发生的中期到达背侧皮质。相反，内皮 VEGFA 的消融改变了皮质中间神经元的数量、它们在皮质内的分布以及与血管的空间接近度。我们首次表明，血管分泌的导向因子在体内促进完整前脑中早期迁移的中间神经元，并确定血管-Vegfa 在这一过程中的新作用。
