AN ANALYSIS OF THE ROLE OF THE CELEGANS SECRETOME ON NEURAL DEVELOPMENT BY RNAI

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 神经系统中的细胞广泛地使用细胞间信号传导线索来适当地延伸神经突，导航到并识别靶细胞，并形成和维持突触接触。从全基因组预测分泌蛋白的能力已经导致了这样的结论，即可能多达三分之一的编码蛋白被分泌到细胞外空间。考虑到神经系统的复杂性，有理由认为许多这些分泌蛋白质在神经系统的模式中起作用。 我们已经从C.线虫基因组我们将采取一种系统的方法，使用RNA干扰（RNAi）来敲除所有7，460种预测的分泌蛋白，并评估这种RNAi对神经发育多个方面的影响。将进行初步表征以鉴定对神经元图案化有影响的分子，并将对这些分子进行二级定量分析。 我们正在使用一种合成的致死筛选方法来表征这些分子的第一，然后我们将检查的产物和突触形态的突变体的基因，表现出的效果。 了解神经系统是如何形成模式的一直是神经生物学的目标。大量的研究已经证明了细胞外蛋白在神经元发育的各个方面的重要性。系统评价所有分泌蛋白功能丧失的影响的能力最近才变得可用。这将为发展的一个极其复杂的部分提供许多新的见解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cells in the nervous system use intercellular signaling cues extensively to properly the extend neurites, navigate to and recognize target cells and form and maintain synaptic contacts. The ability to predict secreted proteins from whole genomes has led to the conclusion that perhaps as much as one third of all proteins encoded are secreted into the extracellular space. Given the complexity of nervous systems it stands to reason that many of these secreted proteins act in the patterning of the nervous system. We have generated a library of predicted secreted proteins from the C. elegans genome. We will take a systematic approach using RNA interference (RNAi) to knockdown of all 7,460 predicted secreted proteins and evaluate the effect of this RNAi on multiple aspects of neural development. A preliminary characterization will be done to identify molecules that have an effect on neuronal patterning, and a secondary level quantitative analysis will be done on those molecules. We are using a synthetic lethal screening approach to characterize these molecules first, and then we will examine the outgrowth and synaptic morphology in mutants for genes that demonstrate an effect. Understanding how the nervous system is patterned has long been a goal of neurobiology. A multitude of studies have demonstrated the importance of extracellular proteins on all aspects of neuronal development. The ability to systematically evaluate the effect of loss of function of all secreted proteins has only recently become available. This will provide many novel insights into an extremely complicated part of development.