Reelin and Migration of Sympathetic Preganglionic Neurons

在完成分裂后，神经元通常会进行长时间的引导迁移，以达到它们在大脑中的适当位置。Reelin基因是小脑正常神经元迁移所必需的，最近发现它在大脑皮层等其他大脑区域也有类似的作用。然而，尽管人们对该基因感兴趣，但尚不清楚它是直接作用于神经元，还是通过其他中介间接作用，或者蛋白质产物是抑制性的还是刺激性的。申请者将使用一种新的系统来检查这个问题。初步数据显示，reelin调节节前交感神经元的迁移，这一现象可以在一个简单的体外切片系统中模拟。该系统将用于：1)定位小鼠神经节前交感神经元的迁移；2)观察Reelin蛋白和迁移的节前神经元之间的时空关系；3)使用阻断抗体和Reelin产生细胞来检测该蛋白的生物活性。由于神经迁移障碍在许多形式的精神发育迟滞中很常见，这项研究应该为这些破坏性障碍的原因提供洞察力。由于分子也与载脂蛋白E和极低密度脂蛋白相互作用，它在阿尔茨海默病中也可能是重要的。

After they finish dividing, neurons typically make long guided migrations to reach their proper loction in the brain. The reelin gene is required for normal neuronal migration on the cerebellum, and more recently it has been found to have similar effects in other brain areas such as the cerebrl cortex. However, despite the interest in this gene, it is not known whether it acts directly upon neurons or more indirectly through other intermediaries, or whether the protein product is inhibitory or stimulatory. The applicant will use a novel system to examine this problem. Preliminary data reveal that reelin regulates the migration of preganglionic sympathetic neurons and that this phenomenon can be mimicked in a simple in vitro slice system. This system will used to: 1) map the migration of pregaglionic sympathetic neurons in mice; 2) look at the spatiotemporal relationship between reelin protein and migration preganglionic neurons; and 3)use blocking antibodies and reelin producing cells to examine the biological activity of this protein. Since disorders of neural migration are common in many forms of mental retardation, this research should provide insights into the causes of these devastating disorders. Since molecules also interacts with apoE and VLDL, it could also be important in Alzheimer's disease.