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 several 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, either alone or in combination, impacts these developmental events. As we determined the temporal and spatial activity of critical transcription factors, we are also cataloging their patterns of expression within the defined cell lineage of the embryo. Although known myogenic factors (HLH-1, UNC-120) are a necessary last step to drive body wall muscle development, the pathway to the stably activating these factors is variable, particularly in the anterior mesodermal lineages. General take aways are that 1) transcriptional cascades involve multiple, short-lived expression bursts persisting over only a couple of cell division in the precursor lineages, 2) closely related gene sequences may be deployed in different lineages to achieve a similar end goal, and 3) the transcription factors encoded by the genes are evolutionarily conserved in driving myogenesis in animals.