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

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2010.07.003 Byline: Ashwin Seetharaman, Philip Cumbo, Nagagireesh Bojanala, Bhagwati P. Gupta Keywords: Nematode; C. elegans; C. briggsae; Vulval development; Signal transduction; Wnt signaling 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[degrees] 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. Article History: Received 9 February 2010; Revised 17 June 2010; Accepted 1 July 2010