Muscle contractions guide rohon-beard peripheral sensory axons.
Muscle contractions guide rohon-beard peripheral sensory axons.
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DOI：
10.1523/jneurosci.2179-09.2009
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发表时间：
2009-10-21
期刊：
影响因子：
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通讯作者：
Halloran MC
中科院分区：
文献类型：
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作者：
Paulus JD;Willer GB;Willer JR;Gregg RG;Halloran MC
在发育过程中，多个分子线索引导神经元轴突到达它们的目标。以前的体外研究表明，机械刺激也可以影响轴突的生长，但机械力是否在体内对轴突的引导作用尚不清楚。我们在活体内研究了肌肉收缩在斑马鱼周围Rohon-Beard(RB)感觉轴突导引中的作用。我们分析了几个通过不同的分子途径影响肌肉收缩的突变，包括titin a(Pik)基因的一个新的突变等位基因，影响hedgehog信号通路的突变，以及一个烟碱型乙酰胆碱受体突变。我们在这些突变体中发现了Rb轴突缺陷，其严重程度似乎与肌肉收缩丧失的程度有关。这些轴突在肌肉和皮肤之间延伸，通常有腹侧轨迹，接触时相互排斥。肌肉突变体中的RB外周轴突是纵向延伸的，而不是腹侧的，并且轴突在接触时不能相互排斥。此外，我们还发现，通过在琼脂糖中植入胚胎来限制肌肉运动，在外周Rb轴突引导中会导致类似的缺陷。这项工作表明，肌肉收缩产生的机械力对于体内正确的感觉轴突寻径是必要的。
Multiple molecular cues guide neuronal axons to their targets during development. Previous studies in vitro have shown that mechanical stimulation also can affect axon growth, however whether mechanical force contributes to axon guidance in vivo is unknown. We have investigated the role of muscle contractions in the guidance of zebrafish peripheral Rohon-Beard (RB) sensory axons in vivo. We analyzed several mutants that affect muscle contraction through different molecular pathways, including a new mutant allele of the titin a (pik) gene, mutants that affect the hedgehog signaling pathway, and a nicotinic acetylcholine receptor mutant. We found RB axon defects in these mutants, the severity of which appeared to correlate with the extent of muscle contraction loss. These axons extend between the muscle and skin and normally have ventral trajectories and repel each other upon contact. RB peripheral axons in muscle mutants extend longitudinally instead of ventrally, and the axons fail to repel one another upon contact. In addition, we showed that limiting muscle movements by embedding embryos in agarose caused similar defects in peripheral RB axon guidance. This work suggests that the mechanical forces generated by muscle contractions are necessary for proper sensory axon pathfinding in vivo.