Abstract
Wnt signaling is tightly regulated during animal development and controls cell proliferation and differentiation. In C. elegans, activation of Wnt signaling alters the activity of the TCF/LEF transcription factor, POP-1, through activation of the Wnt/β-catenin or Wnt/β-catenin asymmetry pathways. In this study, we have identified CACN-1 as a potential regulator of POP-1 in C. elegans larval development. CACN-1/Cactin is a well-conserved protein of unknown molecular function previously implicated in the regulation of several developmental signaling pathways. Here we have used activation of POPTOP, a POP-1-responsive reporter construct, as a proxy for Wnt signaling. POPTOP requires POP-1 and SYS-1/β-catenin for activation in L4 uterine cells. RNAi depletion experiments show that CACN-1 is needed to prevent excessive activation of POPTOP and for proper levels and/or localization of POP-1. Surprisingly, high POPTOP expression correlates with increased levels of POP-1 in uterine nuclei, suggesting POPTOP may not mirror endogenous gene expression in all respects. Genetic interaction studies suggest that CACN-1 may act partially through LIT-1/NLK to alter POP-1 localization and POPTOP activation. Additionally, CACN-1 is required for proper proliferation of larval seam cells. Depletion of CACN-1 results in a loss of POP-1 asymmetry and reduction of terminal seam cell number, suggesting an adoption of the anterior, differentiated fate by the posterior daughter cells. These findings suggest CACN-1/Cactin modulates Wnt signaling during larval development.
Highlights
Wnt signaling is crucial for proper cell fate specification, cell migration, and cell division
POPTOP is expressed in the somatic gonad during L4 POPTOP, which consists of seven POP-1 binding sites and the pes-10 minimal promoter driving the expression of mCherry, has been used in C. elegans as a readout for Wnt signal transduction in various tissues throughout larval development [38]
This rise in activation requires the activating b-catenin SYS-1 and correlates with an increase in POP-1 nuclear localization and a decrease in LIT-1::GFP animals were probed with anti-GFP (LIT-1), suggesting CACN-1 may exert its effects on POPTOP at least partially through LIT-1
Summary
Wnt signaling is crucial for proper cell fate specification, cell migration, and cell division. Wnt signaling drives axial polarization throughout the animal kingdom [1,2], generates attractive and repulsive cues that guide axon migration [3], and induces the activity of Cyclin D1, a regulator of cell cycle progression [4]. In C. elegans, signaling through the canonical and the noncanonical asymmetry pathways results in stabilization and nuclear localization of b-catenin, thereby providing a partner for the TCF/LEF family of transcription factors, and allowing activation of gene expression [6,8,9]. The asymmetry pathway activation of Nemo-like kinase (NLK) regulates nuclear-cytoplasmic cycling of TCF/LEF [8,10]. The C. elegans Wnt signaling pathways utilize several divergent b-catenins (SYS-1, WRM-1, and BAR-1) to regulate a single TCF/LEF homolog, POP-1 [13,14,15,16,17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
