Wnt and FGF signaling in C. elegans vulval cell lineage polarity

The interpretation of extracellular cues leading to the polarization of intracellular components and asymmetric cell divisions is a fundamental part of metazoan organogenesis. The C. elegans vulva, with its invariant cell lineage and interaction of multiple cell signaling pathways, provides an excellent model for the study of cell polarity within an organized epithelial tissue. Herein I discuss the interaction of Wnt and FGF signaling in controlling vulval cell lineage polarity with emphasis on the posterior-most cell that forms the vulva, P7.p.

The mirror symmetry of the C. elegans vulva is achieved by the opposite division orientation of the vulval precursor cells (VPCs) flanking the axis of symmetry. Opposing Wnt signals control the division patterns of the VPCs by controlling the localization of SYS-1/ β-catenin toward the direction of the Wnt gradient. Multiple Wnt signals, expressed at the axis of symmetry, promote the wild-type, anterior-facing, P7.p orientation, whereas Wnts EGL-20 and CWN-1 from the tail and posterior body wall muscle, respectively, promote the daughter cells of P7.p to face the posterior. EGL-20 acts through a member of the LDL receptor superfamily, LRP-2, along with Ror/CAM-1 and Van Gogh/VANG-1. All three transmembrane proteins control orientation through the localization of the SYS-1.

The Fibroblast Growth Factor (FGF) pathway acts in concert with LIN-17/Frizzled to regulate the localization of SYS-1. The source of the FGF ligand is the 1° VPC, P6.p, which controls the polarity of the neighboring 2° VPC, P7.p, by signaling through the sex myoblasts (SMs), activating the FGF pathway. The Wnt, cwn-1, is expressed in the posterior body wall muscle of the worm as well as the SMs, making it the only Wnt expressed on the posterior and anterior sides of P7.p at the time of the polarity decision. Both sources of cwn-1 act instructively to influence P7.p polarity in the direction of the Wnt gradient. The FGF pathway leads to the regulation of cwn-1 transcripts in the SMs. These results illustrate the first evidence of the interaction between FGF and Wnt in C. elegans development and vulval cell lineage polarity as well as highlight the promiscuous nature of Wnt signaling within C. elegans.