Developmental Gene Expression In C elegans

我们对在发育过程中调控细胞命运决定的转录因子感兴趣。我们的模型系统是秀丽隐杆线虫（一种非寄生蠕虫），由于其体积小，易于在实验室培养，解剖简单，增殖迅速和遗传学，被广泛用于发育研究。我们目前对在其他系统中发现的对中胚层模式和肌肉形成重要的转录因子感兴趣。我们已经证明秀丽隐杆线虫的MyoD和Twist转录因子对包括肌肉在内的胚胎后中胚层细胞的形成和模式化很重要。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秀丽隐杆线虫特定肌肉细胞亚群发育中的确切作用。作为我们努力理解细胞分化的一部分，我们已经确定了在细胞周期G1期起作用的三个基因。细胞必须协调细胞周期退出和分化，G1细胞周期因子在这一过程中起重要作用。我们已经证明，周期蛋白E在发育过程中对所有细胞周期都至关重要，而周期蛋白D仅在胚胎后调节细胞周期。最后，我们对基因调控的兴趣引导我们研究秀丽隐杆线虫中的一种RNA编辑形式。被称为ADARs的酶促因子修饰双链mRNA，并可以改变信息的编码区域。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。在与犹他大学的Brenda Bass合作中，我们分离出了缺乏ADAR活性的秀丽隐杆线虫突变体，并通过趋化性测试表明它们在神经元功能方面存在缺陷。这些结果证明了ADAR活性对生物体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.