GENETIC CONTROL OF EMBRYOGENESIS IN C ELEGANS

线虫胚胎发生的遗传控制

基本信息

批准号：
2196841
负责人：
WILLIAM B WOOD
金额：
$ 14.79万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-04-01 至 1998-03-31
项目状态：
已结题

项目摘要

The long term objective of this project is to elucidate mechanisms of determination in animal embryonic development, using the nematode Caenorhabditis elegans as an experimental system. In the C elegans embryo, determination of cell fates is a hierarchical process: the primary determinants are probably localized, maternally derived macromolecules, whose effects are secondarily modified by establishment of sexual identity and by cell interactions controlling expression of embryonic genes that further dictate cell-type determination. This project will continue to investigate the mechanisms of sex determination and the roles of embryonically expressed genes in patterning and cell fate decisions. In the first area, recent work from our laboratory has shown that her-1, the initial major switch gene in the regulatory pathway that controls sex determination, encodes a small secreted polypeptide that exerts its masculinizing effects via transmembrane signalling. To further elucidate her-1 function, the regulation of its male-specific transcription will be investigated, the active form of the her-1 product will be isolated and its primary structure determined, and experiments will be undertaken to identify its receptor by binding assays with embryonic cells in culture. These studies could have eventual health implications for control of human parasitic nematode infections. In a related project, a small region of the X chromosome that appears to be a component of the primary signal for sex determination will be molecularly characterized. In the area of cell-type determination, ongoing large-scale screens using trimethyl-psoralen as a mutagen will be continued, with the goal of saturation for non-maternal-effect mutations that result in specific effects on embryonic patterning. In the course of these screens, several loci (nob genes) have been identified that mutate to cause similar severe posterior patterning defects, and one of these has been shown to be a previously identified homeobox gene (pal-1), homologous to the caudal gene in Drosophila. The remaining nob genes will be cloned for molecular characterization, and their interactions with each other and with other known embryonically expressed and maternal-effect genes will be investigated by genetic as well as molecular methods, in an effort to understand the control of posterior patterning in the embryo. In light of accumulating evidence that all animal embryos employ similar determination mechanisms, these studies are likely to contribute eventually to understanding of human hereditary birth defects and other developmental disorders.

该项目的长期目标是阐明使用线虫的动物胚胎发育中的测定秀丽隐杆线虫作为实验系统。在秀丽隐杆线虫中胚胎，确定细胞命运是一个分层过程：主要决定因素可能是本地化的，母和大分子的作用是由建立来修改的性认同和通过控制表达的细胞相互作用进一步决定细胞类型测定的胚胎基因。这项目将继续调查性别确定的机制以及胚胎表达基因在图案和细胞中的作用命运决定。在第一个领域，我们实验室的最新工作表明，HER-1，控制性别的监管途径中的初始主要开关基因确定，编码一个小的分泌多肽，该多肽发挥作用通过跨膜信号传导男性化的效应。进一步阐明 HER-1功能，其男性特异性转录的调节将是调查，HER-1产品的主动形式将被隔离，并且它确定的主要结构，并将进行实验通过与培养物中的胚胎细胞结合来识别其受体。这些研究最终可能对控制人寄生线虫感染。在一个相关项目中，一个小 X染色体的区域似乎是主要的组成部分性别确定的信号将被分子表征。在细胞类型的区域中，正在进行的大规模屏幕使用将继续进行三甲基 - 丙菌根作为诱变剂，目的是非主效应突变的饱和度导致特定的对胚胎图案的影响。在这些屏幕过程中，有几个已鉴定出基因座（NOB基因），突变会引起类似的严重后构图缺陷，其中之一已被证明是先前鉴定出的同源基因（PAL-1），与尾部同源果蝇中的基因。其余的NOB基因将被克隆用于分子表征及其相互互动以及与其他人的互动已知的胚胎表达和母体效应基因将是通过遗传和分子方法研究了解胚胎中后图案的控制。在光线下累积证据表明所有动物胚胎都采用类似的证据确定机制，这些研究可能有助于最终了解人类遗传出生缺陷和其他发育障碍。