A characteristic property of planar polarity systems is that polarity information in one cell can be transmitted to adjacent cells, a property that helps to align cells with their immediate neighbors. As a result, disrupting the Frizzled system in one cell can cause polarity disruptions up to several cell diameters away. For example, wild-type wing cells point their hairs toward cells that lack Frizzled and away from cells that lack Van Gogh, suggesting that cells can monitor the activity of their neighbors and orient their polarity accordingly [2
]. These results have led to the longstanding idea that Frizzled - a well-known receptor for Wnt ligands - is active in a large-scale gradient that organizes planar polarity across hundreds of cells. However, there is currently no direct evidence for a gradient of Frizzled expression or activity, and the obvious candidates for generating such a gradient, the Wnt ligands, do not appear to be required for planar polarity in Drosophila
In contrast, the Dachsous cadherin and the Four-jointed kinase are expressed in gradients in several tissues that display planar polarity. Dachsous protein at the surface of one cell can bind to Fat on the neighboring cell, an interaction that is thought to inhibit Fat activity [9
]. Therefore, a gradient of Dachsous is predicted to result in lower Fat activity on the proximal side of each cell, even though the distribution of Fat is uniform (Figure ). Notably, flattening or reversing these gradients is sufficient to reorient planar cell polarity, suggesting that the Fat system could provide global direction to the Frizzled pathway [4
]. Consistent with this idea, Frizzled signaling is altered in the absence of Dachsous and Fat and is required for the effects caused by removing Dachsous activity [12
However, other evidence indicates that the Fat system can act independently of the Frizzled pathway to regulate planar polarity. For example, loss of function or ectopic expression of Fat pathway proteins in the Drosophila
abdomen can reorient cell polarity even in tissues that lack Frizzled, and cells mutant for both Dachsous and Flamingo are more defective than cells completely lacking either protein alone, suggesting that these components function at least partly in parallel [14
]. A resolution of this controversy will require identification of the signals that act downstream of Fat, to determine whether these signals regulate the level or localization of Frizzled activity or if they lead to a distinct cellular response.