Interplay between cell cycle regulators and developmental signals in the Caenorhabditis elegans germline.

摘要

The coordination between the cellular decision to proliferate or differentiate is critical to generate tissues during development and maintain them in adults. Coordination defects can lead to abnormal development, congenital deformity and cancer. Regulation of the cell cycle is critical to coordinate a cell's decision, yet our understanding of the molecular mechanisms integrating the cell cycle and development is poor. My thesis focuses on the roles of the core cell cycle regulators in development using the C. elegans germline as a model in vivo system.;Germline proliferation and the self-renewal of germline stem cells (GSCs) are controlled by GLP-1/Notch signaling from the somatic distal tip cells (DTCs) and the RNA-mediated mitosis/meiosis decision network in germ cells. Well-conserved cell cycle regulators, cyclin E/CYE-1 and cyclin-dependent kinase 2/CDK-2, promote cell cycle progression and proliferation during animal development. However, it is not known how developmental signals integrate into the germ cell cycle. My thesis work reveals the developmental functions of CYE-1 and CDK-2 in the C. elegans germline. This work suggests that CYE-1/CDK-2 balances germ cell mitosis and meiosis, and is stem cell regulators.;My work establishes a foundation to determine general mechanisms regulating proliferation versus differentiation decision. The elucidation of the molecular mechanisms will likely shed light on cancer and developmental diseases. Additionally, the discovery of CYE-1/CDK-2 as a stem cell regulator and its working mechanism will impact our understanding of stem cell biology field.