MOLECULAR GENETICS OF NEURAL SPECIFICITY

拟议研究的长期目标是了解 神经特异性的分子基础 人脑是 由大约一千亿个神经元组成 建立了一个复杂而特殊的网络， 通讯细胞 这些神经元是如何识别 从无数的细胞类型中选择合适的伴侣， 为系统做贡献？ 这项建议的目的是 采用分子遗传学方法作为第一步， 回答这个问题。 在线虫中，秀丽隐杆线虫， 神经系统的完整解剖 测定 由于这些详细的信息，突变体 表现出行为缺陷与特定的 神经元形态的改变。 unc-4基因突变 运动，并导致组织的具体变化， 腹神经索 在unc-4突变体中， VA类运动神经元的突触输入被替换为 通常为VB运动神经元保留的神经支配模式。 其他类型的神经元不受unc-4突变的影响。 因此，unc-4基因是建立一个 突触形成的特殊模式。 unc-4基因将会 分离自C.转座子标记技术对线虫进行了研究。 的 将测定unc-4基因的DNA序列， 推导出相应蛋白质的一级结构 产品 UNC-4蛋白的片段将在 细菌并用于制备特异性抗体。 免疫 技术将被用来鉴定内源性UNC-4 蛋白质及其表达的细胞。 与此 生物化学信息，应该可以制定一个 模型来解释UNC-4作用的分子机制。 此外，预期核酸和 从这项工作中得到的免疫探针可以是 用于鉴定同源基因和蛋白质， 在其他更复杂的神经系统中发挥作用。

The long term goal of the proposed research is to understand the molecular basis of neural specificity. The human brain is composed of about 100 billion neurons each of which forms multiple synapes to establish an elaborate yet specific network of communicating cells. How does each of these neurons recognize the appropriate partners from among the myriad cells types that contribute to the system? The objective of this proposal is to employ a molecular genetic approach as a first step toward answering this question. In the nematode, Caenorhabditis elegans, the complete anatomy of the nervous system has been determined. As a result of this detailed information, mutants exhibiting behavioral defects have been correlated with specific alterations in neuronal morphology. Mutations in the unc-4 gene movement and cause specific changes in the organization of the ventral nerve cord. In unc-4 mutants, a characteristic network of synaptic inputs to the VA class of motor neurons is replaced with an innervation pattern normally reserved for VB motor neurons. Other types of neurons are not affected by the unc-4 mutation. Thus, the unc-4 gene is necessary for the establishment of a particular pattern of synapse formation. The unc-4 gene will be isolated from C. elegans by a transposon tagging technique. The DNA sequence of the unc-4 gene will be determined in order to deduce the primary structure of the corresponding protein product. Fragments of the unc-4 protein will be produced in bacteria and used to prepare specific antibodies. Immunological techniques will be employed to identify the endogenous unc-4 protein and the cells in which it is expressed. With this biochemical information, it should be possible to formulate a model to explain the molecular mechanism of unc-4 action. Furthermore, it is expected that the nucleic acid and immunological probes that will be derived from this work can be employed to identify homologous genes and proteins with similar functions in other more complex nervous systems.