Sánchez-Soriano Natalia, Prokop Andreas
Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom.
J Neurosci. 2005 Jan 5;25(1):78-87. doi: 10.1523/JNEUROSCI.2377-04.2005.
The phenomenon of pioneer neurons has been known for almost a century, but so far we have little insights into mechanisms and molecules involved. Here, we study the formation of the Drosophila intersegmental motor nerve (ISN). We show that aCC/RP2 and U motor neurons grow together at the leading front of the ISN. Nevertheless, aCC/RP2 neurons are the pioneers, and U neurons are the followers, because only aCC/RP2 neurons effectively influence growth of the ISN. We also show that this influence depends on the neural cell adhesion molecule homolog FasciclinII. First, ablation of aCC/RP2 has a stronger impact on ISN growth than U ablation. Second, strong growth-influencing capabilities of aCC/RP2 are revealed with a stalling approach we used: when aCC/RP2 motor axons are stalled specifically, the entire ISN (including the U neurons) coarrests, demonstrating that aCC/RP2 neurons influence the behavior of U growth cones. In contrast, stalled U neurons do not have the same influence on other ISN motor neurons. The influence on ISN growth requires FasciclinII: targeted expression of FasciclinII in U neurons increases their influence on the ISN, whereas a FasciclinII loss-of-function background reduces ISN coarrest with stalled aCC/RP2 axons. The qualitative differences of both neuron groups are confirmed through our findings that aCC/RP2 growth cones are wider and more complex than those of U neurons. However, U growth cones adopt aCC/RP2-like wider shapes in a FasciclinII loss-of-function background. Therefore, FasciclinII is to a degree required and sufficient for pioneer-follower interactions, but its mode of action cannot be explained merely through an equally bidirectional adhesive interaction.
先驱神经元现象已为人所知近一个世纪，但迄今为止，我们对其涉及的机制和分子了解甚少。在这里，我们研究果蝇节间运动神经（ISN）的形成。我们发现，aCC/RP2和U运动神经元在ISN的前端共同生长。然而，aCC/RP2神经元是先驱神经元，U神经元是跟随神经元，因为只有aCC/RP2神经元能有效影响ISN的生长。我们还表明，这种影响取决于神经细胞粘附分子同源物FasciclinII。首先，aCC/RP2的消融对ISN生长的影响比U消融更强。其次，我们使用的一种停滞方法揭示了aCC/RP2强大的生长影响能力：当aCC/RP2运动轴突特异性停滞时，整个ISN（包括U神经元）都会共同停滞，这表明aCC/RP2神经元会影响U生长锥的行为。相比之下，停滞的U神经元对其他ISN运动神经元没有同样的影响。对ISN生长的影响需要FasciclinII：在U神经元中靶向表达FasciclinII会增加它们对ISN的影响，而FasciclinII功能丧失背景会减少ISN与停滞的aCC/RP2轴突的共同停滞。通过我们的发现证实了这两个神经元群体的质性差异，即aCC/RP2生长锥比U神经元的更宽且更复杂。然而，在FasciclinII功能丧失背景下，U生长锥会呈现出类似aCC/RP2的更宽形状。因此，FasciclinII在一定程度上是先驱 - 跟随者相互作用所必需且足够的，但其作用方式不能仅仅通过同等双向的粘附相互作用来解释。
