Systematic identification of receptors required for nervous system development in C. elegans

在发育过程中，大脑神经元迁移到合适的位置，并发出细突（轴突和树突）。轴突有时会长很长的距离到达目标区域，在那里它们与其他神经元连接，形成神经元网络。我们正在研究神经元迁移和轴突寻径的分子机制。秀丽隐杆线虫中可用的工具和资源允许大规模筛选策略来识别控制发育过程的基因。在这个建议中，我们计划系统地筛选在神经元迁移过程中起作用的假定受体。我们建立了一个主要未表征的跨膜蛋白（可能是新的受体）的列表，这些蛋白在胚胎发育期间在神经元中表达。我们计划系统地筛选这些基因中的可用突变体，以确定神经元发育所需的潜在新受体。我们预计这将揭示一些基因，这些基因对神经元或轴突向目标迁移很重要。秀丽隐杆线虫中发现的许多基因的强进化保守性确保了我们的发现将对理解包括人类在内的脊椎动物大脑发育过程中的迁移过程具有普遍重要性。

During the development of the brain neurons migrate to their proper locations and send out thin processes (axons and dendrites). Axons grow sometimes over long distances into target regions where they connect to other neurons forming neuronal networks. We are studying the molecular mechanism of neuronal migration and axonal pathfinding. Tools and resources available in C. elegans allow large-scale screening strategies to identify genes controlling developmental processes. In this proposal we plan to screen systematically putative receptors for a role in neuronal migration processes. We established a list of predominantly uncharacterized transmembrane proteins (possibly novel receptors), which are expressed in neurons during embryonic development. We plan to systematically screen available mutants in those genes to identify potentially novel receptors required for neuronal development. We anticipate that this will uncover a number of genes, which are important for the migration of neurons or axons towards their targets. The strong evolutionary conservation of many genes found in C. elegans ensures that our findings will be of general importance for the understanding of migration processes during brain development also in vertebrates including humans.