Song H J, Ming G L, Poo M M
Department of Biology, University of California at San Diego, La Jolla 92093-0357, USA.
Nature. 1997 Jul 17;388(6639):275-9. doi: 10.1038/40864.
Development of the nervous system depends on the correct pathfinding and target recognition by the growing tip of an axon, the growth cone. Diffusible or substrate-bound molecules present in the environment may serve as either attractants or repellents to influence the direction of growth-cone extension. Here we report that differences in cyclic-AMP-dependent activity in a neuron may result in opposite turning of the growth cone in response to the same guidance cue. A gradient of brain-derived neurotrophic factor normally triggers an attractive turning response of the growth cone of Xenopus spinal neurons in culture, but the same gradient induces repulsive turning of these growth cones in the presence of a competitive analogue of cAMP or of a specific inhibitor of protein kinase A. This cAMP-dependent switch of the turning response was also found for turning induced by acetylcholine, but not for the turning induced by neurotrophin-3 (NT-3). Thus, in the presence of other factors that modulate neuronal cAMP-dependent activity, the same guidance cue may trigger opposite turning behaviours of the growth cone during its pathfinding in the nervous system.
神经系统的发育依赖于轴突生长锥的生长尖端进行正确的路径寻找和目标识别。环境中存在的可扩散或与底物结合的分子可作为吸引剂或排斥剂，影响生长锥延伸的方向。我们在此报告，神经元中环磷酸腺苷（cAMP）依赖性活性的差异可能导致生长锥对相同引导信号产生相反的转向。脑源性神经营养因子的梯度通常会触发培养的非洲爪蟾脊髓神经元生长锥的吸引性转向反应，但在存在cAMP竞争性类似物或蛋白激酶A特异性抑制剂的情况下，相同梯度会诱导这些生长锥产生排斥性转向。对于乙酰胆碱诱导的转向，也发现了这种cAMP依赖性的转向反应切换，但对于神经营养因子-3（NT-3）诱导的转向则未发现。因此，在存在其他调节神经元cAMP依赖性活性的因素时，相同的引导信号在神经系统中生长锥路径寻找过程中可能触发相反的转向行为。
