COELOMOCYTES IN C.ELEGANS--CELL FATE DETERMINATION

线虫秀丽隐杆线虫将被用作模型系统，以研究开发过程中的细胞命运规范。这项研究的重点是解决如何在不同的中胚层命运之间做出选择。在高等真核生物中，中胚层的模式化对于正常发育是必不可少的，因为这些细胞有助于血液，器官和结缔组织。这个过程涉及细胞内在和外在因素的复杂相互作用，以便在正确的时间和正确的位置形成不同的组织类型。未能正确指定中胚层的命运可能导致严重的发育缺陷或死亡。由于C.虽然已知线虫是已知的，但是该系统允许在细胞水平上快速表征基因活性。两种方法将被用来解决中胚层图案的问题。首先，将进行遗传筛选以分离改变称为体腔细胞的中胚层细胞的特化的突变。这些细胞为研究非肌肉中胚层的命运提供了极好的机会，因为它们来自谱系的三个不同部分，并且它们在胚胎发生期间非常晚才出生。将使用组织特异性标志物测定体腔细胞特化缺陷。将使用标准遗传和分子技术表征突变和相应基因。基因功能将使用激光消融、镶嵌分析和表达研究来表征。第二，胚胎操作实验，即激光消融，将被执行，以确定细胞内在线索和诱导信号的相对贡献。这些研究有望为深入了解发育过程中细胞命运规范的基本机制提供帮助。此外，由于已知参与类似过程的许多分子在癌细胞中被激活，这项工作可能会增加我们对肿瘤形成和转移的理解。

The nematode Caenorhabditis elegans will be used as a model system to study cell fate specification during development. This research is focused on addressing how choices between different mesodermal fates are made. In higher eukaryotes, patterning of mesoderm is essential for proper development, since these cells contribute to blood, organs, and connective tissues. This process involves the complex interplay of cell intrinsic and extrinsic factors so that the different tissue types are formed at the correct time and in the correct place. Failure to properly specify mesodermal fates can lead to severe developmental defects or death. Since the genome is sequenced and since lineage of all somatic cells of C. elegans are known, this system allows for the rapid characterization of gene activities at a cellular level. Two approaches will be used to address questions of mesodermal patterning. First, genetic screens will be performed to isolate mutations which alter the specification of mesodermal cells called coelomocytes. These cells provide an excellent opportunity to studying non-muscle mesodermal fates since they arise from three different parts of the lineage and they are born very late during embryogenesis. Defects in coelomocyte specification will be assayed using tissue specific markers. The mutations and corresponding genes will be characterized using standard genetic and molecular techniques. Gene function will be characterized using laser ablations, mosaic analyses, and expression studies. Second, embryo manipulation experiments, i.e. laser ablations, will be performed to determine the relative contributions of cell intrinsic cues and inductive signals. These studies are expected to provide insight into the basic mechanisms of cell fate specification during development. In addition, since many of the molecules involved in similar processes are known to be activated in cancer cells, this work may increase our understanding of tumor formation and metastasis.