CONTROL OF EARLY DEVELOPMENT IN C ELEGANS

每一个多细胞有机体发育过程中的一个关键过程是 不同细胞中不同发育命运的特性 早期胚胎。在线虫线虫的胚胎中，如 在许多其他物种的胚胎中，这一过程被认为是 主要由母亲提供的因素控制，这些因素是不同的 在受精卵的早期分裂期间分裂的。除了……之外 母性因素，我们有新的证据表明父母亲提供了因素 也是正常早期发育所必需的。我们建议联合 基因、分子和细胞生物学方法来识别关键的 母亲和父亲的因素，了解特定于家族的因素是如何 区分到特定的细胞，并阐明何时以及如何 这些因素参与了线虫细胞命运的决定 胚胎。 我们发现了一种新的父性效应胚胎致死突变体，spe- 11，这表明精子贡献因子是 受精卵发育正常。两种令人兴奋的可能性是，Spe- 11产物激活卵母细胞或为受精卵提供极性。至 研究spe-11产物的作用，我们将克隆spe-11基因 并分析和定位其基因产物，定义温度- 突变的敏感期，分离第二个位点抑制子，并尝试 通过显微注射精子因子挽救突变受精卵。母性的 我们将重点关注的因素是胚系所需的因素。 发展。P颗粒，这是母体提供的细胞质 分离到胚系卵裂球的结构 早期的部门，是胚系“决定因素”的极佳候选者。 我们正在使用生化技术和我们收集的抗P颗粒 用于纯化和分析颗粒成分的抗体；我们的 长期目标是通过评估它们在生殖系中的功能 遗传学。同时，通过母体效应不孕症的筛查 没有孙子的突变体，我们正在鉴定母体中有缺陷的突变体 对生殖系发育的控制；其中一些因素可能会确定 它们决定了生殖系。最后，我们继续分析 世系特有因素的分离机制。我们有 已经证明微丝(MFS)在 合子极性的产生和对磷颗粒的分离 细菌血统。我们将研究MFS在分区中的作用 体细胞谱系特有的因子，我们将研究几个 MFS参与种族隔离活动的具体机制， 如肌动蛋白-肌球蛋白相互作用和细胞质流动。

A crucial process in the development of every multicellular organism is the specification of different developmental fates in different cells of the early embryo. In embryos of the nematode Caenorhabditis elegans, as in embryos of many other species, this process is thought to be controlled mainly by maternally supplied factors that are differentially partitioned during the early divisions of the zygote. In addition to maternal factors, we have new evidence that paternally supplied factors also are required for normal early development. We propose to combine genetic, molecular, and cell biological approaches to identify crucial maternal and paternal factors, learn how lineage-specific factors are differentially partitioned to specific cells, and elucidate when and how such factors participate in cell-fate determination in C. elegans embryos. We have identified a novel paternal effect embryonic lethal mutant, spe- 11, that demonstrates that a sperm-contributed factor is required for normal zygote development. Two exciting possibilities are that the spe- 11 product activates the oocyte or provides polarity to the zygote. To investigate the role of the spe-11 product, we will clone the spe-11 gene and analyze and localize its gene product, define the temperature- sensitive period of the mutant, isolate second site suppressors, and try to rescue mutant zygotes by microinjecting sperm factors. The maternally supplied factors on which we will focus are those required for germ-line development. P granules, which are maternally supplied cytoplasmic structures that are segregated to the germ-line blastomeres during the early divisions, are excellent candidates for germ-line "determinants". We are using biochemcal techniques and our collection of anti-P-granule antibodies to purify and analyze the composition of the granules; our long-term goal is to assess their function in the germ line through genetics. Concurrently, by screening for maternal effect sterile of grand-childless mutants, we are identifying mutants defective in maternal control of germ-line development; some of these may identify the factors that determine the germ line. Finally, we are continuing our analysis of the mechanism of segregation of lineage-specific factors. We have already demonstrated that microfilaments (MFs) play a critical role in the generation of zygotic polarity and in segregating P granules to the germ lineage. We will investigate the role of MFs in partitioning somatic-lineage-specific factors, and we will investigate several specific mechanisms by which MFs could participate in segregation events, such as actin-myosin interactions and cytoplasmic streaming.