Radial glia regulate vascular patterning around the developing spinal cord.
Radial glia regulate vascular patterning around the developing spinal cord.
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DOI：
10.7554/elife.20253
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发表时间：
2016-11-17
期刊：
影响因子：
7.7
通讯作者：
Stainier DY
中科院分区：
文献类型：
--
作者：
Matsuoka RL;Marass M;Avdesh A;Helker CS;Maischein HM;Grosse AS;Kaur H;Lawson ND;Herzog W;Stainier DY
单个器官周围的血管网络对于器官的发育、维护和功能非常重要；然而，人们对这些网络是如何组装的仍然知之甚少。在这里，我们证明中枢神经系统祖细胞（称为放射状胶质细胞）通过充当负调节器来调节脊髓周围的血管模式。我们发现斑马鱼胚胎中的放射状胶质细胞消融导致脊髓周围的主干血管过度萌芽，并且专门是静脉特性的干血管。从机制上讲，我们确定放射状胶质细胞通过 Vegf 诱饵受体 sFlt1 控制这一过程：sflt1 突变体表现出在放射状胶质细胞消融的幼虫中观察到的静脉过度萌芽，而 sFlt1 过表达可以挽救这一现象。遗传镶嵌分析表明，躯干内皮细胞中的 sFlt1 功能可以限制其过度萌芽。总之，我们的研究结果将中枢神经系统祖细胞确定为关键的血管生成调节因子，决定了脊髓周围脉管系统的精确模式，为发育器官周围血管网络的形成提供了新的见解。 DOI：http://dx.doi.org/10.7554/eLife.20253.001
Vascular networks surrounding individual organs are important for their development, maintenance, and function; however, how these networks are assembled remains poorly understood. Here we show that CNS progenitors, referred to as radial glia, modulate vascular patterning around the spinal cord by acting as negative regulators. We found that radial glia ablation in zebrafish embryos leads to excessive sprouting of the trunk vessels around the spinal cord, and exclusively those of venous identity. Mechanistically, we determined that radial glia control this process via the Vegf decoy receptor sFlt1: sflt1 mutants exhibit the venous over-sprouting observed in radial glia-ablated larvae, and sFlt1 overexpression rescues it. Genetic mosaic analyses show that sFlt1 function in trunk endothelial cells can limit their over-sprouting. Together, our findings identify CNS-resident progenitors as critical angiogenic regulators that determine the precise patterning of the vasculature around the spinal cord, providing novel insights into vascular network formation around developing organs. DOI: http://dx.doi.org/10.7554/eLife.20253.001