Signal transduction pathways and their regulation of transcriptional factors during Caenorhabditis elegans development

An important question in developmental biology is how a single cell divides to produce different types of cells, tissues and organs. Cell-to-cell signaling is an important mechanism to generate differential gene expression patterns. These different gene expression patterns lead to different cell identities and coordinate cellular behaviors. Compared to the number of different cell types present in an animal, there are a limited number of signal transduction pathways. This means that a given pathway must function in combination with other cellular processes to generate a range of different developmental outcomes. Understanding how a single signal transduction mechanism can lead to distinct outcomes is important to understanding developmental diversity.;One source of diversity for signal transduction pathways is from their regulation of transcriptional factors. Different transcriptional factors, combined with different cellular context, will activate differential gene expression patterns. Here I investigate the regulatory relationships between the genes for HOM-C transcriptional factors and the EGF and WNT signaling pathways in a simple binary cell fate decision, the development of the P11/P12 ventral epithelial cells of C. elegans. I show that WNT and EGF signaling can promote the P12 cell fate in the absence of the HOM-C gene egl-5, indicating that egl-5 is not strictly necessary for the P12 fate. I demonstrate that the regulatory relationship between WNT and EGF signaling and HOM-C genes is similar in the posterior body region P12 cell specification and in the mid-body vulval development. However the mechanism is different. Specifically, I find that preventing fusion of the presumptive P12 cell to hyp7 is not sufficient to promote the P12 cell fate in the absence of egl-5. Moreover, I use molecular studies to show that egl-5 expression in the P12 lineage is under dynamic control by factors important for initiation of expression, as well as through autoregulation for maintenance of expression. Overall, this work suggests a model in which a key role for HOM-C genes in P12 development is to ensure a reproducible pattern of cell fates and cellular responses to extracellular signals, rather than directly specifying cell fate. I interpret that WNT and EGF signaling pathways play an instructive role in P12 development.;A second source of diversity for signal transduction pathways is from different signal ligands. I investigate the Eph/ephring signaling pathway in C. elegans germline apoptosis. I show that ephrin ligands EFN-1/VAB-2 and EFN-3 act upon VAB-1/Eph receptor to promote germline apoptosis. Further, I demonstrate that the Eph signaling is dependent on a functional Ras/MAPK pathway. Together, the results suggest that VAB-1/Eph signaling is an upstream trigger that activates the Ras/MAPK pathway to induce physiological germline apoptosis. This function is in contrast to VAB-1/Eph signaling in oocyte maturation. In this case, VAB-1/Eph inhibits the Ras/MAPK pathway and EFN-2 is the primary ligand. These different effects on Ras/MAPK pathway possibly result from the activities of different ligands and cofactors. The results show that the same receptor can trigger different regulatory outputs in a single organ, and illustrate a new example of diversity for signal transduction pathway regulation.