Conserved mechanism of Wnt signaling function in the specification of vulval precursor fates in C. elegans and C. briggsae

Abstract

The C. elegans hermaphrodite vulva serves as a paradigm for understanding how signaling pathways control organ formation. Previous studies have shown that Wnt signaling plays important roles in vulval development. To understand the function and evolution of Wnt signaling in Caenorhabditis nematodes we focused on C. briggsae, a species that is substantially divergent from C. elegans in terms of the evolutionary time scale yet shares almost identical morphology. We isolated mutants in C. briggsae that display multiple pseudo-vulvae resulting from ectopic VPC induction. We cloned one of these loci and found that it encodes an Axin homolog, Cbr-PRY-1. Our genetic studies revealed that Cbr-pry-1 functions upstream of the canonical Wnt pathway components Cbr-bar-1 (beta-catenin) and Cbr-pop-1(tcf/lef) as well as the Hox target Cbr-lin-39 (Dfd/Scr). We further characterized the pry-1 vulval phenotype in C. briggsae and C. elegans using 8 cell fate markers, cell ablation, and genetic interaction approaches. Our results show that ectopically induced VPCs in pry-1 mutants adopt 2° fates independently of the gonad-derived inductive and LIN-12/Notch-mediated lateral signaling pathways. We also found that Cbr-pry-1 mutants frequently show a failure of P7.p induction. A similar, albeit low penetrant, defect is also observed in C. elegans pry-1 mutants. The genetic analysis of the P7.p induction defect revealed that it was caused by altered regulation of lin-12 and its transcriptional target lip-1 (MAP kinase phosphatase). Thus, our results provide evidence for LIN-12/Notch-dependent and independent roles of Wnt signaling in promoting 2 degrees VPC fates in both nematode species.

Anchor cell signaling and vulval precursor cell positioning establish a reproducible spatial context during C. elegans vulval induction

“…Wnt signaling plays many roles in vulva development, including the formation and maintenance of the competence group (Eisenmann et al, 1998;Shemer and Podbilewicz, 2002;Wang et al, 1993), vulval induction (Gleason et al, 2002;Seetharaman et al, 2010) and P7.p polarity (Gleason et al, 2006;Inoue et al, 2004). In particular, two Wnt ligands, lin-44 and mom-2, were previously shown to be expressed in the AC (Inoue et al, 2004), thus providing potential candidates for a positioning signal from the AC to the VPCs.…”

Role of Pleiotropy in the Evolution of a Cryptic Developmental Variation in Caenorhabditis elegans

“…Indeed, quantitative variation in a downstream fluorescent reporter of the EGF/Ras pathway was detected among C. elegans wild isolates despite no change in the resulting cell fates (Figure 1D) [10]. Furthermore, the type and frequency of vulval fate errors following a variety of environmental, genetic, or experimental perturbations differ among Caenorhabditis species and C. elegans wild isolates (Figure 1E–F) [10],[24],[26]–[28]. Due to the broad knowledge of the developmental network, the small number of cells involved and the ease of genetic studies in C. elegans , vulval cell fate patterning is an ideal model to investigate the evolutionary origin and consequences of cryptic variation.…”

-Catenin-Dependent Wnt Signaling in C. elegans: Teaching an Old Dog a New Trick

“…Here we summarize our current understanding of these two C. elegans signaling pathways and the ways they are similar to, and diverge from, Wnt signaling pathways in other species. Although recent work has extended our knowledge of Wnt signaling to other nematode species (Zheng et al 2005;Rudel et al 2008;Tian et al 2008;Lin et al 2009;Owraghi et al 2010;Seetharaman et al 2010;Penigault and Felix 2011a;Wang and Sommer 2011), in this review we will concern ourselves with a survey of Wnt signaling in the established model system C. elegans.…”