Quantitative Differences in Nuclear β-catenin and TCF Pattern Embryonic Cells in C. elegans

Abstract

The Wnt signaling pathway plays a conserved role during animal development in transcriptional regulation of distinct targets in different developmental contexts but it remains unclear whether quantitative differences in the nuclear localization of effector proteins TCF and β-catenin contribute to context-specific regulation. We investigated this question in Caenorhabditis elegans embryos by quantifying nuclear localization of fluorescently tagged SYS-1/β-catenin and POP-1/TCF and expression of Wnt ligands at cellular resolution by time-lapse microscopy and automated lineage tracing. We identified reproducible, quantitative differences that generate a subset of Wnt-signaled cells with a significantly higher nuclear concentration of the TCF/β-catenin activating complex. Specifically, β-catenin and TCF are preferentially enriched in nuclei of daughter cells whose parents also had high nuclear levels of that protein, a pattern that could influence developmental gene expression. Consistent with this, we found that expression of synthetic reporters of POP-1-dependent activation is biased towards cells that had high nuclear SYS-1 in consecutive divisions. We identified new genes whose embryonic expression patterns depend on pop-1. Most of these require POP-1 for either transcriptional activation or repression, and targets requiring POP-1 for activation are more likely to be expressed in the cells with high nuclear SYS-1 in consecutive divisions than those requiring POP-1 for repression. Taken together, these results indicate that SYS-1 and POP-1 levels are influenced by the parent cell’s SYS-1/POP-1 levels and this may provide an additional mechanism by which POP-1 regulates distinct targets in different developmental contexts.

Wnt Signaling Polarizes C. elegans Asymmetric Cell Divisions During Development

“…SYS-1 asymmetry is observed throughout embryogenesis (Bertrand and Hobert, 2009a, Huang et al, 2007, Zacharias et al, 2015, Phillips et al, 2007), consistent with broad function promoting WβA-dependent cell fate. Further, SYS-1 depletion causes gutlessness and promotes the posterior fate of various embryonic ACDs (Bertrand and Hobert, 2009a, Bertrand and Hobert, 2010, Huang et al, 2007, Phillips et al, 2007).…”

“…A second mechanism explaining WβA-driven cell type diversity was identified through lineage tracing of cells expressing fluorescently-tagged SYS-1 and POP-1 and transcriptional fusions of their target genes (Zacharias et al, 2015, Zacharias and Murray, 2016). These time-lapse experiments quantifying gene expression demonstrate that, while sister cells always show asymmetry, their absolute expression level is influenced by the prior expression level in the lineage.…”

Conserved and Exapted Functions of Nuclear Receptors in Animal Development

“…Loss of nhr-67 results in embryonic and L1 lethality [152]. In the embryo, nhr-67 is expressed in the posterior-most daughters of multiple lineages—reminiscent of the function of tll in Drosophila embryonic termini— and appears to be responsive to Wnt regulation [156]. …”

The benefits of local depletion: The centrosome as a scaffold for ubiquitin-proteasome-mediated degradation

“…Recent in vivo observations demonstrate that a range of relative concentrations of various Wnt signaling components including SYS-1 and its cofactor TCF can produce a continuum of signaling strengths throughout C. elegans embryogenesis. 85 The explicit role of centrosome-associated degradation in modulating the dosage of SYS-1 and other clients in various developmental contexts remains a challenge for future studies.…”