Wnts are secreted signaling proteins that regulate cell polarity in many contexts. Wnt signaling between neighboring cells can instructively regulate cell polarity, but how a long-range Wnt signal can regulate polarity at a distance is unclear. To address how cells interpret Wnt gradient information to generate cell polarity, we turned to C. elegans seam cells, which polarize and asymmetrically divide in response to three Wnts: egl-20, cwn-1, and cwn-2. These Wnts are partially redundant in most seam cells despite different expression patterns, and mis-expression experiments suggested that these Wnts may be permissive signals for seam cell polarization (Yamamoto, et. al., 2011). Here, we report that Wnts also have instructive functions in seam cell polarization and that these roles may depend on an unexpected positive feedback reinforcement of asymmetric Wnt and Frizzled localizations to the posterior ends of polarizing cells. We first found that Wnts can instructively regulate seam cell polarity in the absence of the Frizzled homolog LIN-17: Wnt mis-expression in a lin-17 mutant enhances seam cell polarity reversals. This result suggests a permissive function for LIN-17 might obscure an underlying instructive role for Wnt. Based on the finding that EGL-20/Wnt localizes to the posterior ends of many seam cells (Pani and Goldstein, 2018), we hypothesized that asymmetric Wnt enrichment could explain how a long-range Wnt gradient might instruct cell polarity. To investigate the cell biological basis for instructive Wnt signaling, we quantified localization of endogenously tagged Wnts in seam cells prior to their first asymmetric division. We found that EGL-20 and CWN-1 are enriched at the posterior ends of most seam cells, including cells far from the posterior Wnt sources. We discovered that EGL-20/Wnt and MOM-5/Frizzled are reciprocally required for posterior ligand and receptor enrichment in seam cells. We propose that positive feedback can reinforce subcellular asymmetries in Wnt and Frizzled localizations, which allows cells to robustly interpret Wnt gradient information to instruct cell polarity and fates following asymmetric divisions.

Affiliations:
- Biology Department, UNC Chapel Hill, Chapel Hill USA
- Multicellular Organization, National Institute of Genetics, Mishima, JP