Dickson Barry J, Gilestro Giorgio F
Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria.
Annu Rev Cell Dev Biol. 2006;22:651-75. doi: 10.1146/annurev.cellbio.21.090704.151234.
Commissural axons grow along complex pathways toward, across, and beyond the midline of the central nervous system. Taking commissural axons in the vertebrate spinal cord and the Drosophila ventral nerve cord as examples, we examine how commissural axon pathfinding is regulated by the Slit family of guidance cues and their Robo family receptors. We extract several principles that seem likely to apply to other axons and other contexts, such as the reiterative use of the same guidance molecules in distinct pathfinding decisions, the transcriptional specification of a pathway, the posttranscriptional regulation of growth along the pathway, and the possible role of feedback mechanisms to ensure the fidelity of pathfinding choices. Such mechanisms may help explain how a relatively small number of guidance molecules can generate complex and stereotyped wiring patterns. We also highlight the many gaps in our understanding of commissural axon pathfinding and question some widely accepted views. We hope that this review encourages further efforts to tackle these questions, in the expectation that this system will continue to reveal the general principles of axon pathfinding.
连合轴突沿着复杂的路径生长，朝向、穿过并延伸至中枢神经系统的中线。以脊椎动物脊髓和果蝇腹神经索中的连合轴突为例，我们研究了导向线索的Slit家族及其Robo家族受体如何调节连合轴突的路径寻找。我们提炼出了几条似乎适用于其他轴突和其他情况的原则，例如在不同的路径寻找决策中重复使用相同的导向分子、路径的转录特化、沿路径生长的转录后调控，以及反馈机制在确保路径寻找选择准确性方面可能发挥的作用。这些机制可能有助于解释相对少量的导向分子如何产生复杂且刻板的布线模式。我们还强调了我们在理解连合轴突路径寻找方面存在的诸多空白，并对一些被广泛接受的观点提出质疑。我们希望这篇综述能鼓励人们进一步努力解决这些问题，期待这个系统能继续揭示轴突路径寻找的一般原则。
