Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve

Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve
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DOI:
10.1101/gad.322904
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发表时间:
2004-11-15
影响因子:
10.5
通讯作者:
Ruhrberg, C
Ruhrberg, C
中科院分区:
生物学1区
文献类型:
--
作者:
Schwarz, Q;Gu, C;Ruhrberg, C

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发育中的神经元在神经管中准确地定位它们的躯体,与合适的邻居接触,并将轴突投射到它们首选的目标上。利用一系列基因工程小鼠突变体,我们现在证明了面神经的体细胞和轴突的行为是由两种分泌的配体独立调节的,这些配体分别是跨膜受体neuropilin 1 (Nrp1)、信号素Sema3A和血管内皮生长因子VEGF164异构体。虽然Sema3A被认为控制面神经轴突的引导,但我们现在表明它不是面神经体寻路所必需的。反之亦然,我们发现VEGF164不是面部运动神经元轴突引导所必需的,但对其体细胞的正确迁移至关重要。这些观察结果首次表明,VEGF有助于体内的神经元模式,并且一个细胞的不同室室可以通过结构不同的配体来协调共享受体的模式。
Developing neurons accurately position their somata within the neural tube to make contact with appropriate neighbors and project axons to their preferred targets. Taking advantage of a collection of genetically engineered mouse mutants, we now demonstrate that the behavior of somata and axons of the facial nerve is regulated independently by two secreted ligands for the transmembrane receptor neuropilin 1 (Nrp1), the semaphorin Sema3A and the VEGF164 isoform of Vascular Endothelial Growth Factor. Although Sema3A is known to control the guidance of facial nerve axons, we now show that it is not required for the pathfinding of their somata. Vice versa, we find that VEGF164 is not required for axon guidance of facial motor neurons, but is essential for the correct migration of their somata. These observations demonstrate, for the first time, that VEGF contributes to neuronal patterning in vivo, and that different compartments of one cell can be co-ordinately patterned by structurally distinct ligands for a shared receptor.