Embryonic patterning requires many signaling pathways to control cell fates. A fundamental step in development is patterning the body axes. Antero-posterior axis patterning depends on the Wnt pathway, which acts through the transcription factor TCF and its coactivator β-catenin. Classic Wnt targets are transcriptionally activated when Wnt signaling is active through the TCF:β-catenin complex binding to cis regulatory regions and are repressed when Wnt signaling is inactive through TCF binding without β-catenin. In contrast, emerging evidence suggests the existence of direct “opposite” targets, activated by TCF without β-catenin and repressed by TCF:β-catenin.
In the C. elegans embryo, almost all cell divisions are patterned by a Wnt pathway variant, called the Wnt/β-catenin asymmetry pathway, in which nuclear level of POP-1/TCF is higher in the unsignaled anterior sister cell and nuclear level of SYS-1/β-catenin is higher in the signaled posterior sister cell. Many genes expressed during embryogenesis are differentially expressed between anterior and posterior sister lineages. Several genes expressed in posterior lineages are classic Wnt targets, expressed when Wnt signaling is active. On the contrary, the regulation of anterior lineage genes is not well understood. I am testing whether these genes are direct opposite Wnt targets and how they are regulated. RNAi depletion of either POP-1 or SYS-1 shows that these factors are necessary for proper regulation of anterior genes but does not distinguish direct from indirect regulation. I will identify anterior gene enhancers, and determine if these enhancers are bound by POP-1 and if any POP-1-bound sites are necessary for anteriorly biased expression.
This work will clarify mechanisms regulating expression of anterior sister lineage genes in the C. elegans embryo, and may have implications for Wnt pathway regulation of genes expressed in unsignaled cells in other species.