DEVELOPMENTAL GENETICS OF CAENORHABDITIS ELEGANS

这项拟议的研究的总体目标是进一步发展遗传学的艺术 小的自由生活线虫秀丽线虫的分析 已被选为阐明发育的遗传基础的模型 和行为，因为它相对细胞的简单性和它固有的 经典遗传分析和分子遗传分析的优势。一种理解 发育的遗传基础很可能是许多 并可能最终为许多人提供重要信息 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丢失方法 产生线虫遗传马赛克，用来阐明细胞- 特定的基因功能。线虫的马赛克是由 自发性的自由染色体片段或复制的体细胞丢失， 这是除了正常的染色体补充之外存在的。方法 建议使用单元格自治标记各种自由复制 一种标记，可以用来识别携带复制的细胞。 操纵体细胞复制丢失频率的方法也是 建议。 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突起以及 必需基因，由隐性致死突变定义；结构和 将分析纯合子致死细胞在镶嵌动物中的功能。 第三个目标是识别和表征隐性致死突变。 与适用于高分辨率的自由复制相平衡 马赛克分析。本文件所涵盖区域的重叠缺陷 将生成免费复制，以便于映射和 致命一击的互补测试。最终逮捕的表型将是 特色化的。 第四个目标是进一步研究mec-8，这是一种最初由 导致触摸不敏感的突变，但现在表现为 合子胚胎致死等位基因。新的等位基因将被识别和 特征性的和基因外的抑制突变将被研究。这个 第五个目标是克隆和测序mec-8和至少一个必需的 以有趣的遗传马赛克为代表的胚胎基因。 第六个目标是产生、鉴定和表征新的染色体 复制，这应该被证明对平衡隐性致死既有用 突变和镶嵌分析。

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.