DEVELOPMENTAL GENE EXPRESSION IN C ELEGANS

我们对细胞命运的调控很感兴趣 在发育过程中的决心(如神经、肌肉、皮肤)。我们的 模型系统是线虫线虫(一种自由生活的小蠕虫) 它被广泛用于发展研究，因为它的小 大小，易于实验室培养，解剖简单，快速 增殖和遗传。我们工作的一个方面是 转录因子，直接与DNA结合的蛋白质，调节 其他基因的表达。我们目前对以下几个项目感兴趣 转录因子(MyoD、E、Twist和MEF-2) 对肌肉的形成很重要。与安迪博士合作 华盛顿卡内基研究所的Fire研究小组 表明线虫的MyoD和Twist因子是重要的 胚胎后中胚层的形成和图案化。我们 还发现了Twist调控的可能靶基因和 表明Twist可能是一种异源二聚体蛋白，与 另一种称为E蛋白的因子。我们工作的第二个方面 重点介绍了细胞分化和 细胞周期。通常情况下，细胞必须退出细胞周期(停止增殖) 为了区别对待。对其他生物和组织的研究 文化已经证明了分化因素的作用，例如 MyoD在拮抗G1期细胞周期因子(如 细胞周期蛋白和细胞周期蛋白依赖性蛋白激酶)导致细胞周期退出和 差异化。利用MyoD，我们已经鉴定了几种线虫 可能调节G1细胞周期的候选蛋白质 进步。使用我们已有的反向遗传方法 证明了这些因素确实调节了细胞的G1期 线虫体内的细胞周期。令人惊讶的是，只有这些G1调节器 在胚胎后发育过程中的功能表明细胞 线虫胚胎发生过程中的增殖缺乏G1期 细胞周期。

We are interested in the regulation of cell fate determination (e.g. nerve, muscle, skin) during development. Our model system is the nematode C. elegans (a small free-living worm) that is widely used for developmental studies because of its small size, ease of culture in the laboratory, simple anatomy, rapid proliferation, and genetics. One aspect of our work focuses on transcription factors, proteins that bind DNA directly to regulate the expression of other genes. We are currently interested in several transcription factors (MyoD, E, Twist, and Mef-2) that are important for muscle formation. In collaboration with Dr. Andy Fire's group at the Carnegie Institution of Washington we have shown that the C. elegans MyoD and Twist factors are important for the formation and patterning of post-embryonic mesoderm. We have also identified possible target genes of Twist regulation and shown that Twist likely functions as a heterodimeric protein with another factor called an E protein. A second aspect of our work focuses on the connection between cellular differentiation and the cell cycle. Usually, cells must exit the cell cycle (stop proliferating) in order to differentiate. Studies in other organisms and tissue culture have demonstrated a role for differentiation factors, such as MyoD, in antagonizing the action of G1 cell cycle factors (e.g. cyclins and cyclin-dependent kinases) leading to cell cycle exit and differentiation. Using MyoD we have identified several C. elegans proteins that are likely candidates for regulating G1 cell cycle progression. Using reverse genetic approaches we have demonstrated that these factors do indeed regulate the G1 phase of the cell cycle in C. elegans. Surprisingly, these G1 regulators only function during postembryonic developments suggesting that cell proliferation during C. elegans embryogenesis lacks a G1 phase of the cell cycle.