Presentation/Session Information

Session Information

Session Title: Plenary Session 2 Session Type: Plenary
Session Location: Royce Hall Session Time: Thu, Jun 25 3:00PM - 6:00PM

Presentation Information

Program Number: 67 Presentation Time: 4:18PM

Presentation Content

The rich get richer: comprehensive quantitative analysis of nuclear SYS-1/β-catenin and POP-1/TCF in C. elegans embryos identifies a novel memory mechanism for gene expression diversification.AMANDA L. ZACHARIAS, TRAVIS WALTON, ELICIA PRESTON, JOHN ISAAC MURRAY. Genetics Department, University of Pennsylvania, Philadelphia,

Quantitative differences in signaling pathway activity are a powerful potential mechanism for diversifying cell fates during development. However, few examples of this mechanism have been identified in vivo, in part due to the challenges of performing quantitative assays. The purpose of this study was to evaluate whether C. elegans embryos use quantitative differences Wnt pathway activity to regulate gene expression. The conserved Wnt pathway acts repeatedly during development, transcriptionally regulating distinct targets in different stages and cell types (i.e. contexts). This dependence of targets on context could reflect not only interactions with differentially expressed transcription factors, but also quantitative, context-specific differences in the nuclear localization of the Wnt pathway effector transcription factor, POP-1/TCF and its cofactor SYS-1/β-catenin. We investigated the role of Wnt pathway activity in target expression by using time-lapse microscopy and automated lineage tracing of Caenorhabditis elegans embryos to quantify expression of Wnt ligands, target genes, and nuclear localization of POP-1 and SYS-1 in vivo at single cell resolution for all cells throughout embryonic development. Contrary to the exiting binary model, we found reproducible quantitative variability in POP-1 and  SYS-1 across cells. Nuclear levels of SYS-1 are constant over time but concentrations increase due to decreases in nuclear volume. Cells in which Wnt signaling was activated for two or more consecutive cell cycles have higher nuclear SYS-1 concentration and stronger POP-1-mediated transcriptional activation than cells where the parent was not signaled, indicating a “memory” of previous states. We measured the POP-1-dependence of candidate targets and identified over a dozen important developmental regulators as new POP-1 targets. We found that most targets require POP-1 for either activation or repression, but not both. The targets that require POP-1 for activation are preferentially expressed in the cells where Wnt signaling was active for consecutive cell cycles, consistent with a functional role for the quantitative difference we observed. Taken together, these results suggest that the enrichment of nuclear POP-1 and SYS-1 across mitosis provides a cellular memory mechanism to integrate lineage history and allow POP-1 to activate distinct targets in different developmental contexts. Future identification of POP-1, SYS-1 and context factor binding sites will help further refine our understanding of the mechanisms governing context-specific activity.




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