Asymmetric Wnt signaling in C. elegans embryonic development and gene regulation
Wnt signaling plays a key role in the development of the C. elegans embryo as well as the development of all metazoans. In C. elegans, the Wnt/β-catenin asymmetry pathway patterns almost all embryonic divisions after the first five, making it an ideal system to study the pathway and investigate how context controls which target genes are activated in particular cells. We previously utilized an automated lineage tracing approach to uncover enrichment of sys-1/β-catenin, a key Wnt pathway co-regulator, in cells that had a lineage history of consecutive Wnt signaling events. Current work in our lab aims to uncover both the mechanisms of this enrichment and its consequences for Wnt target gene regulation. We used the bipartite cGAL expression system to manipulate Wnt signaling during embryonic development in order to evaluate the current model for the Wnt/β-catenin asymmetry pathway. We mis-expressed Wnt ligand in the anterior of the early embryo to determine if nearby cells can be re-polarized. We are currently investigating the effects of ectopic Wnt expression on β-catenin asymmetry and enrichment and on Wnt dependent transcription, as well as division angles and cell positions.
Another major interest of the laboratory is the structure of Wnt regulated enhancers. We are currently focused on identifying the co-regulatory transcription factors that work with pop-1/TCF to regulate the enhancers of nob-1/php-3, the homologs of Hox12. We have identified ceh-13/Hox1, unc-62/Meis/hth, elt-1/GATA as regulators of distinct individual enhancers of nob-1, with additional evidence that ceh-20/40/Pbx/exd may also contribute. These results expand our understanding of the functions of Wnt signaling during development and expand the gene regulatory network of the early C. elegans embryo.