Endodermal regulation of primordial germ cells

 描述(申请人提供)：原始生殖细胞(PGCs)是成年生殖细胞系的胚胎前体细胞。在胚胎发育的早期，PGCs从体细胞中分离出来，表现出独特的行为和调节。一种保守的PGC行为，在无脊椎动物和脊椎动物中都存在，是与内皮细胞的物理联系。PGC-内胚层相互作用的意义尚不清楚。通过对解剖结构简单的线虫胚胎中的PGCs和内胚层进行实时荧光成像，我们发现了内胚层在重塑PGC内容物中一个意想不到的新角色。具体地说，我们观察到PGCs延伸出大的细胞质小叶，这些小叶被内皮细胞主动地咬掉和消化。内胚层辅助的重塑允许PGCs丢弃细胞成分，如大部分线粒体，我们假设重塑为PGCs即将向成体生殖细胞的过渡做好准备。这一探索性建议的主要目标是建立线虫胚胎作为模型，以研究内胚层-PGC相互作用的目的和机制。我们的具体目标是(1)检验细胞身体吞噬基因的子集促进内胚层辅助的PGC重塑的假设；(2)克隆和鉴定现有的突变体，并寻找新的PGC重塑失败的突变体。这些研究将为确定内胚层辅助的PGC重塑是否对线虫和其他物种的成体生殖细胞功能重要提供基础。此外，我们的发现可能会对概念上类似的重塑事件产生新的见解，例如光感受器外段的脱落和神经元的重塑。

 DESCRIPTION (provided by applicant): Primordial germ cells (PGCs) are embryonic precursors of the adult germ line. At early stages of embryogenesis, PGCs segregate from somatic cells and exhibit distinctive behaviors and regulation. One conserved PGC behavior, which occurs in both invertebrates and vertebrates, is physical association with endodermal cells. The significance of PGC-endoderm interactions is not known. By performing live fluorescent imaging of PGCs and endoderm in the anatomically simple C. elegans embryo, we have discovered an unexpected and novel role for endoderm in remodeling PGC contents. Specifically, we observe that PGCs extend large cytoplasmic lobes, which are actively bitten off and digested by endodermal cells. Endoderm-assisted remodeling allows PGCs to discard cellular components, such as the majority of their mitochondria, and we hypothesize that remodeling prepares PGCs for their impending transition to adult germ cells. The broad goal of this exploratory proposal is to establish the C. elegans embryo as a model to investigate the purpose and mechanism of endoderm-PGC interactions. Our specific goals are to (1) to test the hypothesis that a subset of cell corpse engulfment genes promotes endoderm-assisted PGC remodeling; and (2) to clone and characterize existing mutants, and to identify new mutants, which fail in PGC remodeling. These studies will provide a basis for establishing whether endoderm-assisted PGC remodeling is important for adult germ cell function in C. elegans and other species. In addition, our findings may yield new insights into conceptually analogous remodeling events, such as the shedding of photoreceptor outer segments and the remodeling of neurons.