Wnt signals organize synaptic prepattern and axon guidance through the zebrafish unplugged/MuSK receptor.

Wnt signals organize synaptic prepattern and axon guidance through the zebrafish unplugged/MuSK receptor.
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DOI:
10.1016/j.neuron.2008.12.025
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发表时间:
2009-03-12
期刊:
影响因子:
16.2
通讯作者:
Granato, Michael
Granato, Michael
中科院分区:
医学1区
文献类型:
--
作者:
Jing, Lili;Lefebvre, Julie L.;Gordon, Laura R.;Granato, Michael

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在神经肌肉发育的早期,乙酰胆碱受体(achr)积聚在肌纤维的中心,正是运动生长锥导航和突触最终形成的地方。在这里,我们发现Wnt11r结合到斑马鱼的未插入/MuSK外结构域来组织这个中央肌肉区。如果没有这样的区域,预图像化的achr就不能聚集,并且,正如活细胞成像所显示的那样,生长锥偏离了它们的中心路径。通过诱导拔插/麝香转基因,我们发现中枢肌肉区的组织对于神经突触的形成是必不可少的,但对于AChR预模式和运动生长锥的引导却是必不可少的。最后,我们发现阻断肌纤维中的非规范无序信号会破坏AChR的预模式和生长锥的引导。我们提出Wnt配体激活肌肉纤维中的未插入/MuSK信号,通过一种类似于平面细胞极性通路的机制,限制生长锥引导和AChR预模式到肌肉中心。
Early during neuromuscular development acetylcholine receptors (AChRs) accumulate at the center of muscle fibers, precisely where motor growth cones navigate and synapses eventually form. Here, we show that Wnt11r binds to the zebrafish unplugged/MuSK ectodomain to organize this central muscle zone. In the absence of such zone, prepatterned AChRs fail to aggregate and, as visualized by live cell imaging, growth cones stray from their central path. Using inducible unplugged/MuSK transgenes we show that organization of the central muscle zone is dispensable for the formation of neural synapses, but essential for AChR prepattern and motor growth cone guidance. Finally, we show that blocking non-canonical dishevelled signaling in muscle fibers disrupts AChR prepatterning and growth cone guidance. We propose that Wnt ligands activate unplugged/MuSK signaling in muscle fibers to restrict growth cone guidance and AChR prepatterns to the muscle center through a mechanism reminiscent of the planar cell polarity pathway.
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