Molecular mechanisms of the formation of crossed projetions.

脊椎动物的神经管是由沿圆周和纵向轴向延伸的轴突束组成的正交阵列。神经管的基底板、基底板和鼻翼板等基本结构向上延伸至尾间脑，这一事实提出了神经管中轴突圆周生长存在共同引导机制的可能性。这实际上是；腹侧迁移的翼板轴突，如来自大鼠小脑深部核神经元的传出神经，被底板引导向腹侧中线，分泌有吸引力的趋化信号。越来越多的证据表明，这些周向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。底板还被发现分泌一种扩散的化学驱避剂，这种驱避剂驱使各种背向迁移的轴突远离底板。在分子水平上，虽然netrin- 1似乎在腹向轴突的引导中发挥了全局作用，但除了依赖netrin- 1的机制外，netrin- 1不依赖的机制似乎也参与了背向轴突的引导。化学驱避剂和化学引诱剂与多种生长锥反应性相结合，可能有助于在脊椎动物大脑中建立复杂的神经回路。如上所述，中间靶点的远距离化学吸引在这一过程中起着关键作用。然而，生长的轴突不会在化学引诱剂浓度预计最大的中间目标处停滞。我们发现，最初被从地板上释放的化学引诱剂吸引的后脑的互交轴突，在体外实验中表现出对化学引诱剂穿过地板的反应性丧失。轴突对化学引诱剂的响应性的这种变化可能使发育中的轴突继续向其最终目的地导航。

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.