Endodermal regulation of primordial germ cells

原始生殖细胞的内胚层调节

基本信息

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
项目类别：
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

项目摘要

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（由适用提供）：原始生殖细胞（PGC）是成年生殖系的胚胎前体。在胚胎发生的早期阶段，PGCS与体细胞隔离，并暴露了独特的行为和调节。一种保守的PGC行为，发生在无脊椎动物和脊椎动物中，是与内皮细胞的物理关联。 PGC-内胚层相互作用的意义尚不清楚。通过在解剖学上简单的秀丽隐杆线虫胚胎中对PGC和内胚层进行活荧光成像，我们发现了内胚层在重塑PGC含量中的意外和新颖的作用。具体而言，我们观察到PGC延长了大型细胞质爱，它们被内胚层细胞积极咬伤并消化。内胚层辅助重塑允许PGC丢弃细胞成分，例如其线粒体的大部分，我们假设重塑为PGC做准备，以使其即将过渡到成年生殖细胞。该探索性建议的广泛目标是建立秀丽隐杆线虫胚胎作为研究内胚层 - PGC相互作用的目的和机制的模型。我们的具体目标是（1）检验以下假设：细胞尸体吞噬基因的子集促进了内胚层辅助的PGC重塑；（2）克隆并表征现有的突变体，并识别新的突变体，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重塑是否对于秀丽隐杆线虫和其他物种中的成年生殖细胞功能很重要。此外，我们的发现可能会产生对概念上类似的重塑事件的新见解，例如光感受器外部段的脱落和神经元的重塑。