Endodermal regulation of primordial germ cells

 描述（由申请人提供）：原始生殖细胞（PGCs）是成体生殖系的胚胎前体。在胚胎发生的早期阶段，PGCs从体细胞中分离出来，并表现出独特的行为和调控。一个保守的PGC行为，发生在无脊椎动物和脊椎动物，是物理协会与内胚层细胞。PGC-内胚层相互作用的意义尚不清楚。通过对解剖学上简单的C.在Elegans胚胎中，我们发现了内胚层在重塑PGC含量中的意想不到的和新颖的作用。具体地说，我们观察到PGCs延伸出大的细胞质叶，这些细胞质叶被内胚层细胞主动咬掉并消化。内胚层辅助重塑允许PGCs丢弃细胞成分，如大部分线粒体，我们假设重塑为PGCs即将过渡到成年生殖细胞做好准备。这一探索性建议的广泛目标是建立C。线虫胚胎作为模型，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）测试细胞尸体吞噬基因的子集促进内胚层辅助的PGC重塑的假设;和（2）克隆和表征现有的突变体，并鉴定新的突变体，这些突变体在PGC重塑中失败。这些研究将为确定内胚层辅助的PGC重塑是否对C.线虫和其他物种。此外，我们的研究结果可能会产生新的见解概念上类似的重塑事件，如光感受器外节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.