DEVELOPMENTAL GENETICS OF CAENORHABDITIS ELEGANS

这项研究的总体目标是进一步发展遗传学的艺术。 分析小型自由生活的线虫秀丽隐杆线虫， 被选为阐明发育遗传基础的模型 和行为，因为它相对简单的细胞和其固有的 经典和分子遗传学分析的优势。 的理解 发展的遗传基础可能是基本的， 医学，并可能最终贡献重要的信息，许多 问题，从先天缺陷到衰老。 第一个具体目标是扩展和完善重复损失法 生成C。elegans遗传镶嵌，这是用来阐明细胞， 特定基因功能 C. elegans马赛克是由 游离染色体片段的自发体细胞丢失或复制， 其除了正常的染色体补体之外还存在。 方法 提出了标记各种自由重复与细胞自主 允许识别携带复制的细胞的标记。 还介绍了操纵体细胞复制丢失频率的方法。 提出了 第二个目标是对影响模式的基因进行镶嵌分析 细胞谱系、细胞迁移和神经突起生长的过程， 必需基因，由隐性致死突变定义;结构和 将分析嵌合体动物中纯合致死细胞的功能。 第三个目标是识别和表征隐性致死突变 通过非常适合高分辨率的自由复制来平衡 镶嵌分析 本报告所涉区域的重叠缺陷 将产生免费的副本，以方便映射， 致命病毒的互补测试 终末期阻滞表型将是 表征了 第四个目标是进一步研究mec-8，一个最初由 这些突变赋予触觉不敏感性，但现在的代表是 合子胚胎致死等位基因 新的等位基因有待鉴定， 特征，并将研究基因外抑制突变。 的 第五个目的是克隆MEC-8和至少一种必需的 胚胎基因由有趣的基因嵌合体代表。 第六个目标是产生、鉴定和表征新染色体 重复，这应该被证明对于平衡隐性致死性都是有用的 突变和嵌合体分析。

The overall goal of the proposed research is to further the art of genetic analysis of the small free-living nematode Caenorhabditis elegans, which has been chosen as a model for elucidating the genetic basis of development and behavior because of its relative cellular simplicity and its inherent advantages for classical and molecular genetic analysis. An understanding of the genetic basis of development may well be fundamental to much of medicine and may ultimately contribute important information to many problems, ranging from congenital defects to senescence. The first specific aim is to extend and refine the duplication-loss method of generating C. elegans genetic mosaics, which are used to elucidate cell- specific gene function. C. elegans mosaics are generated by the spontaneous somatic loss of a free chromosome fragment or duplication, which is present in addition to the normal chromosome complement. Methods are proposed for tagging various free duplications with a cell autonomous marker that allows one to identify cells that carry the duplication. Methods for manipulating the frequency of somatic duplication loss are also proposed. The second aim is to conduct mosaic analyses of genes that affect patterns of cell lineage, cell migration and nerve process outgrowth as well as essential genes, defined by recessive lethal mutations; the structures and functions of homozygous lethal cells in mosaic animals will be analyzed. The third aim is to identify and characterize recessive lethal mutations balanced by a free duplication that is well suited for high resolution mosaic analysis. Overlapping deficiencies in the region covered by this free duplication will be generated to facilitate the mapping and complementation testing of the lethals. Terminal arrest phenotypes will be characterized. The fourth aim is to study further mec-8, a gene originally defined by mutations that confer touch insensitivity but which is now represented by zygotic embryonic lethal alleles. New alleles are to be identified and characterized, and extragenic suppressor mutations will be studied. The fifth aim is to clone and sequence mec-8 and at least one essential embryonic gene represented by interesting genetic mosaics. The sixth aim is to generate, identify, and characterize new chromosome duplications, which should prove useful both for balancing recessive lethal mutations and for mosaic analysis.