Rutishauser U, Edelman G M
J Cell Biol. 1980 Nov;87(2 Pt 1):370-8. doi: 10.1083/jcb.87.2.370.
This report describes the influence of neurite fasciculation on two aspects of nerve growth from chick spinal ganglia in vitro: the inhibition of outgrowth by high concentrations of nerve growth factor (NGF) and the preferential growth of neurites toward a capillary tube containing NGF. These studies involved a comparison of cultures of single cells, cell aggregates, and intact ganglia and the use of antibodies against the nerve cell adhesion molecule (CAM) to perturb fasciculation under a variety of conditions. The inhibition of outgrowth, which was observed with ganglia and aggregates but not with single cells, was correlated with a thickening of neurite fascicles. In accord with this observation, anti-CAM, which diminishes fasciculation by inhibiting side-to-side interactions between individual neurites, also partially reversed the inhibition of neurite outgrowth at high NGF concentrations. On the basis of these and other studies, we consider the possibility that neurite bundling causes an increase in the elastic tension of a fascicle without a compensatory increase in its adhesion to substratum. It is proposed that this imbalance could inhibit neurites from growing out from a ganglion and even result in retraction of preexisting outgrowth. In the analysis of NGF-directed growth, it was found that a capillary source of NGF produced a steep but transient NGF gradient that subsided before most neurites had emerged from the ganglion. Nevertheless, the presence of a single NGF capillary caused a dramatic and persistent asymmetry in the outgrowth of neurites from ganglia or cell aggregates. In contrast, processes of individual cells did not appear to orient themselves toward the capillary. The most revealing finding was that anti-CAM antibodies caused a decrease in the asymmetry of neurite outgrowth. These results suggest that side-to-side interactions among neurites can influence the guidance of nerve bundles by sustaining and amplifying an initial directional signal.
高浓度神经生长因子（NGF）对神经突生长的抑制作用，以及神经突向含有NGF的毛细管的优先生长。这些研究涉及对单细胞、细胞聚集体和完整神经节培养物的比较，并使用抗神经细胞黏附分子（CAM）抗体在各种条件下干扰束化。在神经节和聚集体中观察到的生长抑制现象在单细胞中未出现，这与神经突束的增粗有关。与此观察结果一致，抗CAM通过抑制单个神经突之间的侧向相互作用减少束化，在高NGF浓度下也部分逆转了对神经突生长的抑制。基于这些及其他研究，我们考虑神经突成束可能导致束的弹性张力增加而其与底物的黏附没有相应增加的可能性。有人提出这种失衡可能抑制神经突从神经节生长出来，甚至导致已有的生长回缩。在对NGF导向生长的分析中发现，NGF的毛细管源产生了一个陡峭但短暂的NGF梯度，在大多数神经突从神经节中伸出之前就消失了。然而，单个NGF毛细管的存在导致神经节或细胞聚集体的神经突生长出现显著且持续的不对称。相比之下，单个细胞的突起似乎不会朝向毛细管定向。最有启发性的发现是抗CAM抗体导致神经突生长的不对称性降低。这些结果表明，神经突之间的侧向相互作用可以通过维持和放大初始方向信号来影响神经束的导向。
