Motor neurons control blood vessel patterning in the developing spinal cord.
Motor neurons control blood vessel patterning in the developing spinal cord.
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DOI：
10.1038/ncomms14583
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发表时间：
2017-03-06
影响因子：
16.6
通讯作者：
Ruiz de Almodóvar C
中科院分区：
文献类型：
--
作者：
Himmels P;Paredes I;Adler H;Karakatsani A;Luck R;Marti HH;Ermakova O;Rempel E;Stoeckli ET;Ruiz de Almodóvar C
在中枢神经系统内形成精确的血管网络对于确保氧气和营养物的输送以及神经元网络的准确功能至关重要。脊髓的血管化是一个非常典型的过程。然而，在这个器官中控制血管模式的指导线索在很大程度上仍然未知。在这里，我们描述了一个新的神经血管通信机制，控制血管的指导，在发展中的脊髓。我们发现，运动神经元列保持无血管的发育时间窗期间，尽管表达高水平的促血管生成血管内皮生长因子（VEGF）。我们描述了运动神经元表达VEGF捕获受体sFlt 1通过Neuropilin-1依赖的机制。使用VEGF获得的功能的方法在小鼠和运动神经元特异性sFlt 1的功能丧失的方法在鸡，我们表明，运动神经元控制血管图案的自分泌机制，通过自己的sFlt 1的表达，tivalentine运动神经元衍生的VEGF。在中枢神经系统中调节血管模式的指导线索仍然不清楚。在这里，作者在小鼠和鸡的脊髓发育中显示，运动神经元通过自分泌机制控制血管图案，该机制通过其捕获受体sFlt 1的表达滴定VEGF。
Formation of a precise vascular network within the central nervous system is of critical importance to assure delivery of oxygen and nutrients and for accurate functionality of neuronal networks. Vascularization of the spinal cord is a highly stereotypical process. However, the guidance cues controlling blood vessel patterning in this organ remain largely unknown. Here we describe a new neuro-vascular communication mechanism that controls vessel guidance in the developing spinal cord. We show that motor neuron columns remain avascular during a developmental time window, despite expressing high levels of the pro-angiogenic vascular endothelial growth factor (VEGF). We describe that motor neurons express the VEGF trapping receptor sFlt1 via a Neuropilin-1-dependent mechanism. Using a VEGF gain-of-function approach in mice and a motor neuron-specific sFlt1 loss-of-function approach in chicken, we show that motor neurons control blood vessel patterning by an autocrine mechanism that titrates motor neuron-derived VEGF via their own expression of sFlt1. The guidance cues regulating blood vessel patterning in the central nervous system remain unclear. Here, the authors show in mice and chicken developing spinal cord that motor neurons control blood vessel patterning by an autocrine mechanism titrating VEGF via the expression of its trapping receptor sFlt1.