Queensland Brain Institute, The University of Queensland, St Lucia 4072, Queensland, Australia.
Mol Cell Neurosci. 2011 May;47(1):45-52. doi: 10.1016/j.mcn.2011.02.012. Epub 2011 Mar 2.
Correct wiring of the nervous system during development requires axons to respond appropriately to gradients of attractive and repulsive guidance cues. However, the steepness and concentration of these gradients vary in vivo, for instance, with distance from the target. Understanding how these changing conditions affect the navigation strategies used by developing axons is important for understanding how they are guided over long distances. Previous work has shown that cyclic nucleotide levels determine whether axons are attracted or repelled by steep gradients of the same guidance cue, but it is unknown whether this is also true for shallow gradients. We therefore investigated the guidance responses of rat superior cervical ganglion (SCG) axons in both steep and shallow gradients of nerve growth factor (NGF). In steep gradients we found that cyclic nucleotide-dependent switching occurred, consistent with previous reports. Surprisingly however, we found that in shallow NGF gradients, cyclic nucleotide-dependent switching did not occur. These results suggest that there may be substantial differences in the way axons respond to gradient-based guidance cues depending on where they are within the gradient.
在发育过程中，神经系统的正确布线要求轴突对吸引和排斥导向线索的梯度做出适当的反应。然而，这些梯度的陡度和浓度在体内会发生变化，例如，与靶标之间的距离有关。了解这些不断变化的条件如何影响发育中的轴突所使用的导航策略对于理解它们如何在长距离内被引导是很重要的。以前的工作表明，环核苷酸水平决定了轴突是被同一导向线索的陡峭梯度吸引还是排斥，但尚不清楚这是否也适用于浅梯度。因此，我们研究了大鼠颈上神经节（SCG）轴突在神经生长因子（NGF）的陡峭和浅梯度中的导向反应。在陡峭的梯度中，我们发现了与以前的报告一致的环核苷酸依赖性转换。然而，令人惊讶的是，我们发现，在浅 NGF 梯度中，环核苷酸依赖性转换并没有发生。这些结果表明，轴突对基于梯度的导向线索的反应方式可能因它们在梯度中的位置而有很大的不同。
