Blood vessels and neurons grow often side by side. However, the molecular and cellular mechanisms underlying their parallel development remain unclear. Here, we report that a subpopulation of secondary motoneurons extends axons ventrally outside of the neural tubes and rostrocaudally as a fascicle beneath the dorsal aorta (DA) in zebrafish. We tried to clarify the mechanism by which these motoneuron axons grow beneath the DA and found that Vegfc in the DA and Vegfr3 in the motoneurons were essential for the axon growth. Forced expression of either Vegfc in arteries or Vegfr3 in motoneurons resulted in enhanced axon growth of motoneurons over the DA. Both vegfr3 morphants and vegfc morphants lost the alignment of motoneuron axons with DA. In addition, forced expression of two mutant forms of Vegfr3 in motoneurons, potentially trapping endogenous Vegfc, resulted in failure of growth of motoneuron axons beneath the DA. Finally, a vegfr3 mutant fish lacked the motoneuron axons beneath the DA. Collectively, Vegfc from the preformed DA guides the axon growth of secondary motoneurons.

译文

血管和神经元经常并排生长。然而,它们平行发展的分子和细胞机制仍不清楚。在这里,我们报告了次级运动神经元的亚群在斑马鱼的背主动脉 (DA) 下方的束中向神经管的腹侧和尾部延伸轴突。我们试图阐明这些运动神经元轴突在DA下生长的机制,并发现DA中的Vegfc和运动神经元中的Vegfr3对于轴突生长至关重要。动脉中Vegfc或运动神经元中Vegfr3的强制表达导致DA上运动神经元的轴突生长增强。vegfr3形变和vegfc形变都失去了运动神经元轴突与DA的排列。此外,在运动神经元中强迫表达两种突变形式的Vegfr3,可能捕获内源性Vegfc,导致DA下方的运动神经元轴突生长失败。最后,vegfr3突变鱼在DA下方缺少运动神经元轴突。总的来说,来自预先形成的DA的Vegfc引导次级运动神经元的轴突生长。

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