The C. elegans Germline: A Test Tube for Cell and Developmental Biology

摘要 胚胎发育的最早阶段是由mRNAs、蛋白质和细胞器引导的，由 母系种系。当胚胎从母体控制切换到合子控制时，机制被部署以清除 母体在完成其功能后从胚胎中提取的mRNAs。其分子机制的研究进展 母体信使核糖核酸的清除尚不完全清楚，但在该领域引起了极大的兴趣。我们最近 发现一种高度保守的RNA结合蛋白是母体清除mRNA所必需的 线虫。值得注意的是，我们发现了许多与这种蛋白质相关的mRNAs 卵母细胞中的(SPN-4)在受精后迅速失稳和清除。我们正在检验这样一种假设 SPN-4通过与CCR4-NOT的结合清除其在体细胞分裂球中的许多相关mRNA 在mRNA不稳定中起作用的死烯基酶。指导下一代科学家是一项 NIH长期支持这一R35奖项及其前身R01的核心组成部分和好处。在.期间 在这个研究项目的过程中，PI指导了各个级别的科学家-从本科生到 致教职员工。线虫分子系统为培训年轻科学家进行 假设驱动的研究。在20℃下的世代时间为3.5天。虫体为透明生殖细胞， 可以直接观察配子和胚胎，以及卵母细胞发育、减数分裂成熟、 和受精。完整的基因组序列和注释良好的数据库有助于分子分析。 CRISPR-Cas9基因组编辑的方法很强大，通常由本科生进行 在我们的实验室里。许多发育控制基因的进化保守确保了广泛的 我们的发现与人类生物学的相关性。这一努力对今年的有效性产生了实质性的好处 资助研究计划，以及更广泛地为科学工作者做出贡献。这项管理工作 家长奖的补充部分旨在指导一名本科生，他一直在PI的 他是一名实验室医生，致力于生物医学研究。这次培训将使她为申请做好准备。 在完成本科学位课程后进入研究生院攻读博士学位。

Summary The earliest stages of embryonic development are guided by mRNAs, proteins, and organelles provided by the maternal germline. As the embryo switches from maternal to zygotic control, mechanisms are deployed to clear maternal mRNAs from the embryo after they have completed their functions. The molecular mechanisms of maternal mRNA clearance are incompletely understood but are of intensive interest for the field. We recently discovered that a highly conserved RNA-binding protein is required for maternal mRNA clearance in the nematode Caenorhabditis elegans. Remarkably, we found many mRNAs that are associated with this protein (SPN-4) in oocytes are rapidly destabilized and cleared after fertilization. We are testing the hypothesis that SPN-4 clears many of its associated mRNAs in somatic blastomeres through its association with the CCR4-NOT deadenylase, which functions in mRNA destabilization. Mentoring the next generation of scientists has been a central component and benefit of NIH’s longstanding support for this R35 award and its predecessor R01. During the course of this research program, the PI has mentored scientists at every level—from undergraduate students to faculty. The C. elegans molecular system provides an ideal format for training young scientists to conduct hypothesis-driven research. The generation time is 3.5 days at 20°C. The worms are transparent and germ cells, gametes, and embryos can be directly observed, as can the process of oocyte development, meiotic maturation, and fertilization. The complete genome sequence and a well-annotated database facilitates molecular analysis. Methods for CRISPR-Cas9 genome editing are robust and are routinely conducted by undergraduate students in our laboratory. The evolutionary conservation of many developmental control genes ensures the wide relevance of our findings to human biology. This effort has had substantial benefits for the effectiveness this funded research program, as well as for more broadly contributing to the scientific workforce. This administrative supplement to the parent award seeks to mentor an undergraduate student, who has been working in the PI’s laboratory and who is committed to a career in biomedical research. This training will position her well for applying to graduate school to pursue a PhD degree upon completion of her undergraduate degree program.