Systematic Vertebrate Functional Genomics

描述（由申请人提供）：脊椎动物基因组含有预测的 10万个基因，大部分功能未知。的最新发展 斑马鱼中基于吗啉代的基因敲除技术打开了 在脊椎动物模型中基于序列的全基因组功能分配。 我们建议探索控制基本的分子机制， 脊椎动物胚胎形成图案和器官形成的生物过程 在发育过程中，细胞与细胞之间的通讯是至关重要的。我们 将把这项研究的重点放在生物功能的系统分配给一个 一组100-200个假定的分泌蛋白质，以确定这些蛋白质中的关键参与者。 细胞间胚胎信号级联。 我们将通过以下具体目标实现这一目标： 艾姆岛分泌性蛋白质吗啉核心数据库的建立。基因 将通过分析预测的分泌蛋白来选择编码预测的分泌蛋白的蛋白质。 斑马鱼基因组和EST数据库。针对这些基因的吗啉代将被 生成并检查以下生物过程中的功能： Aim II.早期胚胎和神经发育所需的分泌蛋白的分离 模式化Aim III.心血管疾病所需分泌蛋白的分离 和感觉器官的形成。目标四。所需分泌蛋白的分离 消化器官的形成和功能。 脊椎动物模式和器官所需分子的鉴定 形成对于理解遗传学具有重要意义。 这些过程中的缺陷。此外，这些信号蛋白， 对于体内发育，将是至关重要的条件， 体外器官形成。斑马鱼提供了第一个综合分析 以整个脊椎动物的基因组为模板。

DESCRIPTION (provided by applicant): The vertebrate genome contains a predicted 100,000 genes, most of unknown function. The recent development of morpholino-based gene knockdown technology in zebrafish has opened the door to the genome-wide assignment of function based on sequence in a model vertebrate. We propose to explore the molecular mechanisms that control fundamental vertebrate embryonic processes of patterning and organ formation, biological problems in which cell-cell communication is critical during development. We will focus this study on the systematic assignment of biological function to a set of 100-200 putative secreted proteins to identify key players in these intercellular embryonic signaling cascades. We will accomplish this goal through the following specific aims: Aim I. Development of a secreted protein morpholino core database. Genes encoding predicted secreted proteins will be selected through analysis of the zebrafish genomic and EST database. Morpholinos targeted to these genes will be generated and examined for function in the following biological processes: Aim II. Isolation of secreted proteins required for early embryonic and neural patterning. Aim III. Isolation of secreted proteins required for cardiovascular and sensory organ formation. Aim IV. Isolation of secreted proteins required for digestive organ formation and function. The identification of molecules required for vertebrate patterning and organ formation has critical implications for the understanding of genetic deficiencies in these processes. In addition, these signaling proteins, crucial for development in vivo, will be crucial to the establishment of conditions for in vitro organ formation. The zebrafish offers the first comprehensive analysis of these processes using as template an entire vertebrate genome.