Angiogenesis in the developing cerebral cortex accompanies cortical neurogenesis. However, the precise mechanisms underlying cortical angiogenesis at the embryonic stage remain largely unknown. Here, we show that radial glia-derived vascular cell adhesion molecule 1 (VCAM1) coordinates cortical vascularization through different enrichments in the proximal and distal radial glial processes. We found that VCAM1 was highly enriched around the blood vessels in the inner ventricular zone (VZ), preventing the ingrowth of blood vessels into the mitotic cell layer along the ventricular surface. Disrupting the enrichment of VCAM1 surrounding the blood vessels by a tetraspanin-blocking peptide or conditional deletion of Vcam1 gene in neural progenitor cells increased angiogenesis in the inner VZ. Conversely, VCAM1 expressed in the basal endfeet of radial glial processes promoted angiogenic sprouting from the perineural vascular plexus (PNVP). In utero, overexpression of VCAM1 increased the vessel density in the cortical plate, while knockdown of Vcam1 accomplished the opposite. In vitro, we observed that VCAM1 bidirectionally affected endothelial cell proliferation in a concentration-dependent manner. Taken together, our findings identify that distinct concentrations of VCAM1 around VZ blood vessels and the PNVP differently organize cortical angiogenesis during late embryogenesis.

中文翻译：

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径向神经胶质细胞衍生的 VCAM1 通过近端和远端径向过程中的不同富集来调节皮质血管生成。

发育中的大脑皮层中的血管生成伴随着皮层神经发生。然而，胚胎阶段皮质血管生成的确切机制在很大程度上仍然未知。在这里，我们展示了径向胶质细胞衍生的血管细胞粘附分子 1 (VCAM1) 通过近端和远端径向胶质过程中的不同富集来协调皮质血管化。我们发现 VCAM1 在内心室区 (VZ) 的血管周围高度富集，防止血管沿心室表面向内生长到有丝分裂细胞层。通过四跨膜蛋白阻断肽或神经祖细胞中 Vcam1 基因的条件性缺失破坏血管周围 VCAM1 的富集增加了内部 VZ 的血管生成。反过来，VCAM1 在径向神经胶质过程的基底尾足中表达，促进了神经周围血管丛 (PNVP) 的血管生成。在子宫内，VCAM1 的过度表达增加了皮质板中的血管密度，而 Vcam1 的敲低则相反。在体外，我们观察到 VCAM1 以浓度依赖性方式双向影响内皮细胞增殖。综上所述，我们的研究结果表明 VZ 血管周围不同浓度的 VCAM1 和 PNVP 在晚期胚胎发生过程中以不同的方式组织皮质血管生成。我们观察到 VCAM1 以浓度依赖性方式双向影响内皮细胞增殖。综上所述，我们的研究结果表明 VZ 血管周围不同浓度的 VCAM1 和 PNVP 在晚期胚胎发生过程中以不同的方式组织皮质血管生成。我们观察到 VCAM1 以浓度依赖性方式双向影响内皮细胞增殖。综上所述，我们的研究结果表明 VZ 血管周围不同浓度的 VCAM1 和 PNVP 在晚期胚胎发生过程中以不同的方式组织皮质血管生成。