Reciprocal regulation of Wnt, receptor and Dvl localizations during cell polarization

Migrating cells use multiple mechanisms to interpret signaling gradients and establish polarity. However, how non-migrating cells interpret such gradients remains poorly understood. In C. elegans, the polarity of asymmetrically dividing seam cells is redundantly regulated by three Wnt proteins: CWN-1, CWN-2, and EGL-20. Here, we show that these Wnts, their receptors, and Dishevelled (Dvl) proteins localize asymmetrically to the posterior side of seam cells in an interdependent manner. The receptors and Dvl colocalize in Wnt-dependent, membrane-associated puncta resembling signalosomes. These findings support positive-feedback mechanisms that links Wnt localization to cell polarity. Because posteriorly expressed CWN-1 and EGL-20 have instructive roles in seam cell polarity, this mechanism may help cells interpret their gradients. In contrast, despite its anterior expression, CWN-2 localizes posteriorly, suggesting that intrinsic polarity cues also contribute to Wnt localization. Together, these findings suggest that feedback integrates Wnt gradients with intrinsic polarity cues to robustly orient cell polarity.