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Molecular mechanisms of the formation of crossed projetions.

交叉投影形成的分子机制。

基本信息

批准号：
09044305
负责人：
MURAKAMI Fujio
金额：
$ 5.7万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09044305/
关键词：
floor plate chemoattraction chemorepulsion culture netrin axon guidance development rat ニューロトロフィン

项目摘要

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.

脊椎动物的神经管是由一个正交阵列的轴突束延伸沿着圆周和纵向轴线。事实上，神经管的基本结构，如底板，基板和侧板延伸到间脑尾侧，提出了一种可能性，即在神经管中有共同的指导机制，周向生长轴突。这实际上已经被证明是腹侧迁移的底板轴突，如从大鼠小脑深核神经元的传出被底板引导向腹侧中线，分泌有吸引力的趋化性信号。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中起着至关重要的作用。在分子水平上，netrin-1在腹侧定向轴突的导向中起着全局性的作用，而netrin-1的非依赖性机制和netrin-1的依赖性机制也参与了背侧定向轴突的导向。化学排斥剂和化学引诱剂与各种生长锥反应性的组合可用于在脊椎动物脑中建立复杂的神经元回路。如上所述，中间靶点的长距离化学吸引在此过程中起关键作用。然而，生长的轴突不会在预期化学引诱物浓度最大的中间目标处停滞。我们发现，连合轴突在后脑，最初吸引了从底板释放的化学引诱剂，失去反应的化学引诱剂在跨底板在体外。轴突对化学引诱物的反应性的这种变化可能使发育中的轴突能够继续向其最终目的地导航。