GENETIC ANALYSIS OF E2F FUNCTION DURING DEVELOPMENT

控制细胞分裂周期是正常动物的重要组成部分 发展在增殖组织中，细胞周期的进展 确保细胞分裂伴随着生长。相反，终端 分化通常在细胞周期停滞之前， 停止扩散。决定是扩散还是留下 在细胞周期的G1期最常进行静止。 体细胞必须正确地管理这一决定，以便正确地 保持体内平衡这种管理需要对细胞进行调节 控制G1-S过渡的循环机械。其中包括基因 扩增阳性细胞周期效应物如细胞周期蛋白D1，和 肿瘤抑制因子pRB和p16等负效应子突变。 这些分子是控制细胞的分子通路的一部分 细胞周期对细胞外的正性和负性效应物的反应 细胞生长 调节这些分子的一个主要目标是 ES 2F/DP异二聚体转录因子家族。E2 F/DP/1/s控制 生长和DNA复制所需基因的表达。最近 结果表明，E2 F/DP功能的扰动在体外和 在体内也可以是致癌的。 E2 F/DP及其已知的上游调控因子在果蝇中都是保守的 黑腹，我们可以应用复杂的遗传方法， E2 F/DP功能分析。在果蝇中，dE 2F/DDP是 正常发展。因此，控制细胞命运的发育信号可能 通过改变E2 F/DP活性来调节细胞生长和细胞周期进程。的 该计划的目标是：1）从遗传学上鉴定新的果蝇 调节dE 2F/DDP活性的基因，因此可能调节 细胞周期的G1-S转换，以及2）了解dE 2F/dDP 调节体内转录以及这如何影响细胞周期控制 在发展过程中。

Controlling the cell division cycle is an essential part of normal animal development. In proliferating tissues, progression through the cell cycle assures that cell division accompanies growth. In contrast, terminal differentiation is typically preceded by cell cycle arrest and the cessation of proliferation. The decision to proliferate or remain quiescent is most often made during the G1 phase of the cell cycle. Somatic cells must correctly manage this decision in order to properly maintain homeostasis. Such management requires regulation of the cell cycle machinery controlling the G1-S transition. This includes gene amplification of positive cell cycle effectors such as cyclin D1, and mutation of negative effectors such as tumor suppressors pRB and p16. These molecules are part of a molecular pathway that controls the cell cycle in response to both positive and negative extracellular effectors of cell growth. A major target of regulation of these molecules is the ES2F/DP family of heterodimeric transcription factors. E2F/DP/1/s control the expression of genes require for growth and DNA replication. Recent results indicate that perturbations of E2F/DP function both in vitro and in vivo can also be oncogenic. E2F/DP and its known upstream regulators are all conserved in Drosophila melanogaster, where we can apply sophisticated genetic approaches to an analysis of E2F/DP function. In Drosophila, dE2F/dDP is required for normal development. Thus, developmental signals that control cell fate may regulate growth and cell cycle progress via altering E2F/DP activity. The goals of this proposal are 1) to genetically identify novel Drosophila genes that regulate the activity of dE2F/dDP and therefore may regulate the G1-S transitions of the cell-cycle, and 2) to understand how dE2F/dDP regulates transcription in vivo and how this affects cell cycle control during development.