CONTROL OF EARLY DEVELOPMENT IN C ELEGANS

单细胞胚胎是如何产生在胚胎中看到的各种组织的？ 成年生物仍然是一个中心未解决的问题， 发展 线虫C.像许多物种一样， 主要由母体提供的因素引导。 我的实验室 利用C. elegans来识别一些 控制这个过程的基因。 我们已经筛选了 编码规范所需的母本成分的基因， 一种特殊的细胞类型，即生殖细胞系的发育。 我们专注于 生殖系，因为它不是生存能力和突变动物所必需的 缺乏生殖细胞的人很容易识别。 我们已经分离出了导致母体效应不育或 “无孙子”表型：由 杂合母体本身是可育的，但产生不育后代。 我们的筛选已经确定了令人惊讶的几个基因：六个mes（用于母系- 效应不育）基因座，由23个突变定义。 五个特征位点 他们似乎属于两个阶级。 MES-1突变母体产生的胚胎 在分裂过程中， 生成生殖系创始细胞。 由此产生的幼虫缺乏生殖系 祖细胞，并含有额外的身体肌肉细胞。 而反观 MES-2、MES-3、MES-4和MES-6母体的后代经历正常的 胚胎发生，但显示严重缺陷，在胚胎后增殖， 生殖系，导致配子体减少100-1000倍 在生殖细胞中。 我们提出的实验将解决以下问题 问题：mes-1突变是否会导致生殖系创始细胞 跟随它的姐妹肌肉祖先的命运吗 这是空值吗 表型，或者更严重的等位基因影响早期的分配事件， 导致胚胎死亡 造成的扩散缺陷 mes-2、mes-3、mes-4和mes-6中的突变反映了缺陷性决定 生殖细胞系或生殖细胞无法执行其 血统？ 这些mes基因产物是生殖细胞系所必需的吗？ 体细胞性腺？ 除了表型分析，我们将克隆和 分子分析MES-1、MES-3、MES-4和MES-6。 通过 免疫定位他们的基因产物，我们将了解是否有任何是 在早期胚胎发生过程中分配到生殖系， 胚粒成分。 最后，我们将筛选和表征 其他MES基因座中的突变。 我们的研究将阐明， 定位和功能的母体因素，参与 产生功能性生殖系。

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.