Developmental Control of the Cell Cycle

描述(由申请人提供)：确定正常细胞周期控制的机制对于我们理解发育和肿瘤发生是至关重要的。在发育过程中，细胞的增殖是通过协调细胞周期和生长的进程来进行的。相反，细胞周期停滞发生在终末分化之前，而且常常是终末分化所必需的。在发育完成后，细胞增殖和细胞周期停滞也受到高度调控：成人组织中的干细胞受到严格的细胞周期控制，静止的细胞也是如此，只有在特定刺激下才会增殖。在上述任何一种情况下，细胞周期控制的崩溃都可能产生严重的后果，并导致癌症典型的无调控生长。该项目的长期目标是阐明发育计划如何影响细胞周期进程，这一过程仍然知之甚少。在这个建议中，我们关注控制G1-S转换的基因表达机制，因为这是大多数细胞决定是否进入或退出细胞周期的时候。与公共健康相关：细胞增殖是所有生物体生物学的一个基本方面，由一系列高度协调的细胞生物学事件控制，称为细胞周期，指导基因组的准确复制和遗传。对动物发育过程中细胞周期事件的详细分子描述对于我们理解细胞增殖控制以及这种控制在癌症等疾病中如何出错至关重要。

DESCRIPTION (provided by applicant): Determining the mechanisms of normal cell cycle control is critical for our understanding of both development and oncogenesis. During development, cell proliferation occurs by coordinating progress through the cell cycle with growth. Conversely, cell cycle arrest occurs prior to, and is often necessary for, terminal differentiation. Cell proliferation and cell cycle arrest are also highly regulated after the completion of development: stem cells in adult tissues are under tight cell cycle control, as are quiescent cells that only proliferate in response to particular stimuli. Breakdowns in cell cycle control in any of these circumstances can have drastic consequences and contribute to the deregulated growth typical of cancer. The long term objective of this project is to elucidate how developmental programs affect cell cycle progression, a process that remains poorly understood. In this proposal we focus on gene expression mechanisms that control the G1-S transition because this is when most cells decide whether to enter or to exit the cell cycle. PUBLIC HEALTH RELEVANCE: Cell proliferation is a fundamental aspect of the biology of all organisms, and is controlled by a highly orchestrated series of cell biological events termed the cell cycle that directs the accurate duplication and inheritance of the genome. A detailed molecular description of cell cycle events during animal development is critical for our understanding of cell proliferation control, and how such control goes awry in diseases like cancer.