Developmental Gene Expression In C elegans

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

Our interests are in gene regulation and developmental regulation. Over this past year, our focus has been on understanding mesodermal cell fate specification and male fertility using forward and reverse genetics in the nematode C. elegans. Anterior lineages that give rise to body wall muscle also generate sever other non-muscle cells and blast cells that undergo post-embryonic developmental fates. In teasing out the transcription factors that are both necessary and sufficient for body wall muscle specification and differentiation, we have uncovered a number of transcription factor also required for several non-muscle cell fates. Using a variety of tools and genetic approaches, we have explored various mutant and/or RNAi-mediated reduction-in-function approaches to sort out as single cell resolution how the loss of each factor, ether alone or in combination, impacts these developmental events. In addition, we continued our long-term collaboration with the Hanover Lab (NIH) to explore further the role of the post-translational modification, O-GlcNAcylation, on development. More specifically, how loss of O-GlcNAc cycling impacts male fertility. Interestingly, the catalytic function of the O-GlcNAc transferase, encoded by the gene ogt-1, is not required for restoring fertility in loss-of-function ogt-1 mutants and mutant rescue can be achieved with expression of transgenes that is limited to the hypodermic. This suggests OGT-1 serves a non-catalytic function in the hypodermis impacting male fertility and mating behavior.