Molecular mechanisms of the formation of crossed projetions.

脊椎动物神经管由沿周轴和纵轴延伸的轴索的正交排列组成。神经管的基本结构，如底板、基底板和翼板一直延伸到尾侧间脑，这一事实提出了这样一种可能性，即神经管中存在着共同的周向生长轴突的引导机制。这实际上被证明是腹侧迁移的翼板轴突，例如来自大鼠小脑深核的传出轴突被底板引导向腹侧中线，分泌出吸引人的趋化信号。越来越多的证据表明，这些环状轴突和底板细胞之间的相互作用在引导轴突穿过中线方面起着至关重要的作用。在分子水平上，尽管网织蛋白-L似乎在腹侧定向轴突的引导中起着全局性的作用，但除了网织蛋白-L依赖的机制外，网织蛋白-L非依赖的机制似乎也参与了背侧定向轴突的引导。化学物质和化学诱导剂与各种生长锥反应性相结合，可能有助于在脊椎动物的大脑中建立复杂的神经元电路。如上所述，中间靶标的远程化学吸引在这一过程中起着关键作用。然而，生长中的轴突并不会在化学吸引剂浓度最大的中间靶点停滞。我们发现，后脑中的连合轴突最初被从底板释放的趋化物质所吸引，但在体外穿过底板时，显示出对化学吸引物质失去了反应性。轴突对化学诱导剂反应的这种变化可能使发育中的轴突能够继续导航到它们的最终目的地。

The vertebrate neural tube is composed of an orthogonal array of axonal tracts extending along circumferential and longitudinal axes. The fact that the basic structures of the neural tube such as the floor plate, basal plate and alar plate extend up to the caudal diencephalon raises the possibility that there is common guidance mechanisms for circumferentially growing axons in the neural tube. This actually has turned out to be the ; ventrally migrating alar plate axons such as the efferent from the deep cerebellar nuclei neurons of the rat are guided towards the ventral midline by the floor plate, secreting an attractive chemotropic signal. Evidence has been accumulating that interactions between these circumferential axons and floor plate cells play a crucial role in guiding axons across the midline. The floor plate was also found to secrete a diffusible chemorepellent(s), which drives a variety of dorsally migratingaxons away from the floor plate.At the molecular level, while netrin-l appears to play a global role in the guidance of ventrally directed axons, netrin-l - independent mechanisms, in addition to netrin-l - dependent mechanism, also appear to be involved in the guidance of dorsally directed axons. Chemorepellents and chemoattractants in combination with a variety of growth cone resposiveness may serve to establish complicated neuronal circuitry in the vertebrate brain.As described above, long-range chemoattraction by intermediate targets plays a key role in this process. Growing axons, however, do not stall at the intermediate targets where the chemoattractant concentration is expected to be maximal. We found, commissural axons in the metencephalon, initially attracted by a chemoattractant released from the floor plate, were shown to lose responsiveness to the chemoattractant in crossing the floor plate in vitro. Such changes in axon responsiveness to chemoattractants may enable developing axons to continue to navigate toward their final destinations.