CONTROL OF EARLY DEVELOPMENT IN C ELEGANS

单细胞胚胎如何产生不同的组织阵列 成体生物体仍然是人类面临的主要问题之一 发展。在线虫中，就像在许多物种中一样，这个过程 主要是由母亲提供的因素决定的。我的实验室正在处理 利用线虫强大的遗传学优势来鉴定一些 控制这一过程的基因。我们已经筛选出了基因突变 编码规范所需母体成分的基因和 发育出一种特定的细胞类型，即生殖系。我们一直专注于 生殖系，因为它不是生存和突变动物所必需的 缺乏生殖细胞很容易被识别出来。 我们已经分离出了导致母性效应不孕的突变 “无孙子”表型：纯合突变型两性人 杂合子母亲本身是可以生育的，但会产生不育的后代。 我们的筛查发现了令人惊讶的几个基因：六个MES(代表母体- 效应不育)基因座，由23个突变定义。这五个特征基因座 似乎属于两个阶层。MES-1突变母亲产生的胚胎 在分裂过程中显示细胞质分裂的缺陷 产生生殖系创始细胞。由此产生的幼虫缺乏胚系 祖细胞，并含有额外的身体肌肉细胞。相比之下， MES-2、MES-3、MES-4和MES-6母亲的后代经历正常 胚胎发生，但在胚胎后增殖中显示出严重缺陷 生殖系，导致无性生殖成虫数量减少100-1000倍 在生殖细胞中。我们提议的实验将解决以下问题 问题：MES-1基因突变是否会导致生殖系创始细胞 追随它的妹妹，肌肉祖细胞的命运？这是空的吗？ 表型，或者更严重的等位基因是否会影响较早的分割事件和 会导致胚胎死亡吗？是否由以下因素引起的扩散缺陷 MES-2、MES-3、MES-4和MES-6的突变反映了有缺陷的确定 或者生殖细胞不能执行它们的 血统？这些MES基因产物是胚系所必需的，还是 体细胞性腺？除了表型分析，我们还将克隆和 对MES-1、MES-3、MES-4和MES-6进行了分子分析。穿过 他们的基因产物的免疫定位，我们将了解是否有 在早期胚胎发生期间被分割到生殖系，以及是否有 胚芽颗粒成分。最后，我们将筛选并描述 其他MES基因座的突变。我们的研究将阐明这一性质， 参与母性因子的定位和功能 产生了一个有功能的生殖系。

How the one-cell embryo generates the diverse array of tissues seen in adult organisms remains one of the central unsolved problems in development. In the nematode C. elegans, as in many species, this process is guided mainly by maternally supplied factors. My lab is taking advantage of the powerful genetics available in C. elegans to identify some of the genes that control this process. We have screened for mutations in genes that encode maternal components required for the specification and development of a specific cell type, the germ line. We have focussed on the germ line because it is not required for viability and mutant animals lacking germ cells are easily identified. We have isolated mutations that result in maternal-effect sterility or a "grandchildless" phenotype: homozygous mutant hermaphrodites produced by heterozygous mothers are themselves fertile but produce sterile progeny. Our screens have identified surprisingly few genes: six mes (for maternal- effect sterile) loci, defined by 23 mutations. The five characterized loci appear to belong to two classes. Embryos produced by mes-1 mutant mothers display defects in cytoplasmic partitioning during the division that generates the germ-line founder cell. The resulting larvae lack germ-line progenitor cells and contain extra body muscle cells. In contrast, the progeny of mes-2, mes-3, mes-4, and mes-6 mothers undergo normal embryogenesis, but show severe defects in post-embryonic proliferation of the germ line, resulting in agametic adults with 100-1000-fold reductions in germ cells. Our proposed experiments will address the following questions: Do mutations in mes-1 cause the germ-line founder cell to follow the fate of its sister, a muscle progenitor? Is this the null phenotype, or do more severe alleles affect earlier partitioning events and lead to embryonic lethality? Do the proliferation defects caused by mutations in mes-2, mes-3, mes-4, and mes-6 reflect defective determination of the germ line or an inability of the germ cells to execute their lineage? Are these mes gene products required in the germ line or in the somatic gonad? In addition to phenotype analysis, we will clone and molecularly analyze mes-1, mes-3, mes-4, and mes-6. Through immunolocalization of their gene products, we will learn whether any are partitioned to the germ line during early embryogenesis and whether any are germ-granule components. Finally, we will screen for and characterize mutations in additional mes loci. Our studies will elucidate the nature, localization, and function of maternal factors that participate in generating a functional germ line.