Developmental Gene Expression In C elegans

Diabetes, Digestive, Kidney Diseases

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Abstract

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.