Developmental Gene Expression In C elegans

Diabetes, Digestive, Kidney Diseases

Investigators

Linked publications & trials

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. 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. One of our major accomplishments this past year was studying the transcription factor CeMyoD. Although important for muscle formation in the nematode, we had previously shown this gene product was not necessary for cells to adopt a muscle fate during development in C. elegans. To further define the exact role of this transcription factor, we ectopically expressed CeMyoD in the early nematode embryo and found that it was sufficient to convert all early blastomeres to a muscle-like fate. The sufficiency of CeMyoD alone to direct cells into the muscle lineage illustrated its potency and revealed a level of evolutionary conservation in function that had not previously been appreciated. Moreover, these experiments revealed a remarkable degree of plasticity of the early embryonic cells to be reprogrammed with regards to cell fate choice. We have begun to use our ability to convert all cells in the C. elegans embryo into muscle in order to profile gene expression during myogenic differentiation. In collaboration with the Hanover Lab in NIDDK, we have continued to explore the role of nutrient sensing in development. Using knockout alleles of genes in C. elegans that regulate the addition and removal of sugar residues on nucleocytoplasmic proteins, we found that the hexosamine pathway influences the developmental decision of growth versus diapause in C. elegans. C. elegans may offer a fascile genetic system to tease apart the subtle roles of the hexosamine pathway in normal development and disease.