Developmental Gene Expression In C elegans

我们感兴趣的是转录因子在细胞发育过程中决定细胞命运的调节作用。我们的模型系统是线虫线虫(一种非寄生蠕虫)，它因其体积小、易于实验室培养、解剖简单、快速繁殖和遗传学而被广泛用于发育研究。我们目前对几个转录因子感兴趣，这些转录因子在其他系统中被确定为对中胚层模式和肌肉形成具有重要作用。我们已经证明线虫MyoD和Twist转录因子对于包括肌肉在内的胚胎后中胚层细胞的形成和模式是重要的。通过研究这些基因突变导致的表型，我们开始确定它们在调节线虫特定肌肉细胞亚群发育中的确切作用。作为我们理解细胞分化的努力的一部分，我们已经确定了三个在细胞周期的G1期起作用的基因。细胞必须协调细胞周期退出和分化，而G1期细胞周期因子在这一过程中起着重要作用。我们已经证明，细胞周期蛋白E对发育过程中的所有细胞周期都是必不可少的，而细胞周期蛋白D只有在胚胎后期才能调节细胞周期。最后，我们对基因调控的兴趣引导我们研究线虫的一种RNA编辑形式。被称为ADAR的酶因子可以修饰双链mRNA，并可以改变消息的编码区。这些活动被认为允许额外水平的基因调控，可能是对环境或细胞刺激的反应。与犹他大学的布伦达·巴斯合作，我们分离了缺乏ADAR活性的线虫突变体，并通过趋化试验表明它们在神经元功能方面存在缺陷。这些结果证明了ADAR活动对生物发育和生存的重要性。

We are interested in transcription factors that function in the regulation of cell fate determination during development. Our model system is the nematode C. elegans (a non-parasitic 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. We are currently interested in several transcription factors that have been identified in other systems as important for mesoderm patterning and muscle formation. We have shown that the C. elegans MyoD and Twist transcription factors are important for the formation and patterning of post-embryonic mesodermal cells including muscle. By studying the phenotypes that result from mutations in these genes we are beginning to define their exact roles in regulating the development of specific subsets of muscle cells in C. elegans. As part of our efforts to understand cellular differentiation, we have characterized three genes that function in the G1 phase of the cell cycle. Cells must coordinate cell cycle exit with differentiation and G1 cell cycle factors are important for this process. We have shown that cyclin E is essential for all cell cycle during development whereas cyclin D functions only post-embryonically to regulate the cell cycle. Finally, our interests in gene regulation have led us to the study a form of RNA editing in C. elegans. Enzymatic factors known as ADARs modify double stranded mRNA and can change the coding region of the message. These activities are thought to allow an additional level of gene regulation, perhaps in response to environmental or cellular stimuli. In collaboration with Brenda Bass at the University of Utah we have isolated C. elegans mutants that lack ADAR activity and have shown that they have deficiencies in neuronal function as assayed by chemotaxis tests. These results demonstrate the importance of ADAR activities for organismal development and survival.