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. In collaboration with Dr. Andy Fire's group at the Carnegie Institution of Washington 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. In addition, one of the mutants we study, a semi-dominant allele of Twist, has interesting parallels to Twist mutations in humans that result in Saethre-Chotzen syndrome. This syndrome is associated with craniofacial and other developmental defects. Our results in C. elegans suggest that certain human Twist alleles are functioning as dominant negative proteins, a notion not previously considered. Our C. elegans mutants also provide a starting point for genetic screens to identify other factors operating in the regulatory hierarchy controlling mesoderm development. The nematode offers the opportunity to study the transcriptional regulation of mesoderm development with single cell resolution which will allow us to make important contributions to the understanding of human development and disease.
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