脉络丛
生物
斑马鱼
室周器官
血管生成
细胞生物学
血管内皮生长因子A
旁分泌信号
血脑屏障
壁细胞
神经科学
血管内皮生长因子C
中枢神经系统
内皮干细胞
血管内皮生长因子
癌症研究
受体
遗传学
血管内皮生长因子受体
体外
基因
作者
Sweta Parab,Olivia A Card,Qiyu Chen,Michelle America,Luke D. Buck,Rachael E Quick,William Horrigan,Gil Levkowitz,Benoît Vanhollebeke,Ryota Matsuoka
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2023-05-16
卷期号:12
摘要
Fenestrated and blood-brain barrier (BBB)-forming endothelial cells constitute major brain capillaries, and this vascular heterogeneity is crucial for region-specific neural function and brain homeostasis. How these capillary types emerge in a brain region-specific manner and subsequently establish intra-brain vascular heterogeneity remains unclear. Here, we performed a comparative analysis of vascularization across the zebrafish choroid plexuses (CPs), circumventricular organs (CVOs), and retinal choroid, and show common angiogenic mechanisms critical for fenestrated brain capillary formation. We found that zebrafish deficient for Gpr124, Reck, or Wnt7aa exhibit severely impaired BBB angiogenesis without any apparent defect in fenestrated capillary formation in the CPs, CVOs, and retinal choroid. Conversely, genetic loss of various Vegf combinations caused significant disruptions in Wnt7/Gpr124/Reck signaling-independent vascularization of these organs. The phenotypic variation and specificity revealed heterogeneous endothelial requirements for Vegfs-dependent angiogenesis during CP and CVO vascularization, identifying unexpected interplay of Vegfc/d and Vegfa in this process. Mechanistically, expression analysis and paracrine activity-deficient vegfc mutant characterization suggest that endothelial cells and non-neuronal specialized cell types present in the CPs and CVOs are major sources of Vegfs responsible for regionally restricted angiogenic interplay. Thus, brain region-specific presentations and interplay of Vegfc/d and Vegfa control emergence of fenestrated capillaries, providing insight into the mechanisms driving intra-brain vascular heterogeneity and fenestrated vessel formation in other organs.
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