Endodermal regulation of primordial germ cells

原始生殖细胞的内胚层调节

• 批准号: 9107473
• 负责人: Jeremy Nance
• 金额: $ 25.17万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-13 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9107473
• 关键词: Actins; Adult; Affect; Apoptotic; Behavior; Biological; Bite; Caenorhabditis elegans; Cannibalism; Cell Communication; Cell physiology; Cell surface; Cells; Cytoplasm; Defect; Digestion; Eating; Embryo; Embryonic Development; Endoderm; Endoderm Cell; Event; Excision; Exhibits; Fertility; Future; Gastrointestinal tract structure; Genes; Genetic Screening; Genome; Germ Cells; Germ Lines; Goals; Gonadal structure; Health; Hour; Image; Invertebrates; Lead; Left; Life; Lobe; Mediating; Mitochondria; Modeling; Mutation; Nematoda; Neurons; Oranges; Organelles; Phosphatidylserines; Photoreceptors; Process; Regulation; Role; Signal Transduction; Site; Somatic Cell; Staging; Sterility; Structure of primordial sex cell; Surface; Teratoma; Testing; Vertebrates; base; cell behavior; egg; fluorescence imaging; imaging genetics; insight; migration; mutant; novel; polymerization; prevent; programs; protein expression; research study; response; sperm cell; tool; tumor

 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.

 描述（由申请人提供）：原始生殖细胞（PGC）是成体生殖系的胚胎前体。在胚胎发生的早期阶段，PGC 与体细胞分离并表现出独特的行为和调节。无脊椎动物和脊椎动物中都存在一种保守的 PGC 行为，即与内胚层细胞的物理关联。 PGC-内胚层相互作用的重要性尚不清楚。通过对解剖学简单的秀丽隐杆线虫胚胎中的 PGC 和内胚层进行实时荧光成像，我们发现内胚层在重塑 PGC 内容物中具有意想不到的新颖作用。具体来说，我们观察到 PGC 延伸出大的细胞质叶，这些叶被内胚层细胞主动咬掉和消化。内胚层辅助重塑允许 PGC 丢弃细胞成分，例如大部分线粒体，我们假设重塑为 PGC 即将向成体生殖细胞的转变做好准备。该探索性提案的总体目标是建立秀丽隐杆线虫胚胎作为模型来研究内胚层-PGC相互作用的目的和机制。我们的具体目标是（1）检验细胞尸体吞噬基因的子集促进内胚层辅助的 PGC 重塑的假设； (2)克隆和表征现有突变体，并鉴定在PGC重塑中失败的新突变体。这些研究将为确定内胚层辅助的 PGC 重塑是否对秀丽隐杆线虫和其他物种的成体生殖细胞功能重要提供基础。此外，我们的研究结果可能会对概念上类似的重塑事件产生新的见解，例如光感受器外节的脱落和神经元的重塑。