Control of neuronal migration by Fasciclin II and Rasputin

在大脑发育过程中，神经细胞必须迁移相当长的距离才能到达最终位置，然后才能与其他神经细胞正确连接。尽管许多不同的信号影响着这一过程，但高等哺乳动物的复杂性使得确定特定蛋白质如何控制大脑内的细胞运动变得困难。作为一种替代策略，更简单的昆虫神经系统可以用来模拟特定类型的蛋白质如何影响细胞行为，为测试相关蛋白质在高等动物中的作用提供框架。该项目将利用昆虫制剂的独特优势来确定一类重要的细胞表面受体“Ig-CAMS”的作用，这种受体存在于所有神经系统中，但其功能知之甚少。延时成像和荧光标记将用于确定不同的ig - cam如何控制不同的细胞运动模式。然后，分子和生化方法的结合将用于测试新发现的“适配器”蛋白质的作用，这些蛋白质在特定时间和地点控制ig - cam的作用。这些研究的结果将揭示这些蛋白质类别在更复杂的生物体（包括人类大脑）中如何发挥作用的新原理。该项目将探索神经细胞引导的一个重要方面，它在控制大脑的形成中起着重要作用。由于昆虫模型系统相对便宜且易于操作，因此拟议的研究将为来自各种背景的学生和教育工作者提供宝贵的培训机会，包括缺乏先前研究经验的本科生。这笔拨款还将支持鼓励妇女和未被充分代表的少数民族参与科学发现的持续努力。该项目的最终目标将是改善目前对发育中的神经系统中控制细胞迁移的基本机制的了解。

During brain development, nerve cells must migrate considerable distances to reach their final locations before they can connect properly to other nerve cells. Although many different signals affect this process, the complexity of higher mammals has made it difficult to determine how specific proteins control cell movements within the brain. As an alternative strategy, simpler insect nervous systems can be used to model how particular types of proteins affect cell behavior, providing the framework for testing the role of related proteins in higher animals. This project will exploit the unique advantages of insect preparations to define the role of an important class of cell surface receptors called "Ig-CAMS", which are found in all nervous systems but whose functions are poorly understood. Time-lapse imaging and fluorescent labeling will be used to determine how different Ig-CAMs control distinct patterns of cell movement. A combination of molecular and biochemical methods will then be used to test the role of newly discovered "adapter" proteins that govern the effects of Ig-CAMs at specific times and places. The results of these studies will reveal new principles about how these protein classes function in more complex organisms, including the human brain. This project will explore an important aspect of nerve cell guidance that plays a major role in controlling the formation of the brain. Because insect model systems are relatively inexpensive and easy to manipulate, the proposed studies will provide valuable training opportunities for students and educators from a variety of backgrounds, including undergraduates lacking prior research experience. This grant will also support ongoing efforts to encourage participation by women and underrepresented minorities in scientific discovery. The ultimate goal of this project will be improve current knowledge about the fundamental mechanisms that control cell migration in the developing nervous system.