DEVELOPMENTAL GENE EXPRESSION IN C ELEGANS

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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.