MOLECULAR GENETIC ANALYSIS OF DEVELOPING SYNAPSES

描述(逐字摘自申请人的摘要)：主要方式为 神经细胞之间的相互通信是通过释放 化学突触的神经递质。大脑的处理能力 信息依赖于准确可靠地形成突触连接 在数百种不同类型的神经元之间。此应用程序被定向 发展对调节突触的过程的分子理解 队形。我们已经创造了突触囊泡蛋白-GFP融合并表达了 在线虫C.的谷氨酸能机械感觉神经元亚群中。 使我们能够在光水平上可视化突触前特化的优雅 活体动物的分辨率。使用这些转基因动物，我们已经分离出 线虫的突变体，其形成能力受到损害 神经元间突触特化。我们建议进一步分析这些 突变体，特别是专注于超微结构特征的 与遗传损伤相关的异常。其次，我们提出了 对其中几个突变体的基因进行分子克隆。分子 克隆这些基因中的第一个表明它编码一个大的蛋白质 与脊椎动物大脑中表达的一种蛋白质同源。第三，我们建议 鉴定出的基因产物的详细分子遗传学特征 通过我们的基因分析来评估它们在突触过程中的作用 发展。而线虫的突触发生可能没有线虫中的 脊椎动物，在C. 优雅的人应该奠定一个基本的脚手架，在上面整合复杂性 与更普遍的和可能保守的突触原则相关 发展。

DESCRIPTION (Verbatim From the Applicant's Abstract): The primary means by which nerve cells communicate with each other is through the release of neurotransmitter at chemical synapses. The ability of the brain to process information depends on synaptic connections forming precisely and reliably between hundreds of different types of neurons. This application is directed towards developing a molecular understanding of processes that regulate synapse formation. We have created synaptic vesicle protein-GFP fusions and expressed these in subsets of glutamatergic mechanosensory neurons in the nematode C. elegans enabling us to visualize presynaptic specializations at light level resolution in live animals. Using these transgenic animals, we have isolated mutants of C. elegans that are compromised in their ability to form interneuronal synaptic specializations. We propose to further analyze these mutants, particularly concentrating on ultrastructural characterization of abnormalities associated with the genetic lesions. Secondly, we propose molecular cloning of the genes lesioned in several of these mutants. Molecular cloning of the first of these genes suggests it encodes a large protein with homology to a protein expressed in the vertebrate brain. Thirdly, we propose the detailed molecular genetic characterization of the gene products identified through our genetic analyses to assess their roles in the process of synapse development. While synaptogenesis in C. elegans likely is less complex than in vertebrates, analysis of the molecules participating in the process in C. elegans should lay a basic scaffold on which to integrate the complexities associated with more general and likely conserved principles of synaptic development.