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

总结

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.