CELLULAR AND MOLECULAR MECHANISMS OF SYNAPTOGENESIS

这个项目将研究细胞和分子机制， 管理突触连接的建立和完善 模型系统，果蝇神经肌肉接头。最新研究 在这个系统中表明轴突引导和突触发生涉及 作用于生长锥体的多个令人厌恶和吸引人的信号。 传出生长和神经肌肉标记物的机制 在胚胎和幼虫的发育过程中，将使用 内源性绿色荧光蛋白果蝇新品系 (GFP)表达。详细的时间推移形态计量学研究 将制作生长锥体，测试对几个细胞的共振， 基因和分子操作。有很好的证据表明 神经肌肉系统的形态可塑性，对 神经支配程度和突触活动的改变。这个 运动神经元茎的细化和可塑性的机制将是 通过对胚胎和胚胎中正在发育的突触进行生命成像测试 Lavae，以应对神经肌肉活动改变的情况 从药理上或遗传上，以及对去神经的反应 或改变神经支配方案。此外，候选基因的 调节神经肌肉发育所需的功能 突触可塑性将在F1突变筛选中确定。 最后，作为反向遗传学研究的一部分，4200 P元素增强剂 对检测器插入片段进行筛选，以寻找表达模式 神经肌肉系统发育。共鉴定了20个果蝇品系 在肌肉纤维和/或亚群中的表达具有特异性 胚胎突触发生过程中的神经元。我们将完成一项 正在进行的这些增强子探测器线的分子表征， 包括对由以下原因导致的突变表型的详细分析 P元素镶件的切除。

This project will examine the cellular and molecular mechanisms that govern the establishment and refinement of synaptic connections in a model system, the Drosophila neuromuscular junction. Recent studies in this system indicate that axon guidance and synaptogenesis involve multiple repulsive and attractive signals that act on the growth cones. The mechanisms of efferent outgrowth and neuromuscular taget selection will be examined in developing embryos and larvae using new Drosophila lines with endogenous Green Fluorescent Protein (GFP) expression. Detailed time-lapse morphometric studies of the growth cones will be made, testing the resonses to several cellular, genetic, and molecular manipulations. There is good evidence for morphological plasticity in the neuromuscular system, in response to alterations of the degree of innervation and synaptic activity. The mechanisms of motoneuron arbor refinement and plasticity will be tested by vital imaging of the developing synapses in both embros and lavae, in response to situations where neuromuscular activity is altered pharmacologically or genetically, as well as in response to denervation or altered innervation protocols. Also, candidate genes whose functions are needed to mediate neuromuscular development and synaptic plasticity will be identified in a F1 mutagenesis screen. Finally, as part of a revers genetic study, 4200 P-element enhancer detector inserts were screened for expression patterns in the developing neuromuscular system. 20 Drosophila lines were identified with specificity of expression in subsets of muscle fibers and/or neurons during embryonic synaptogenesis. We will complete an ongoing molecular characterization of these enhancer detector lines, including a detailed analysis of mutant phenotypes that result from excision of the P-element inserts.