Dachsous-Dependent Asymmetric Localization of Spiny-Legs Determines Planar Cell Polarity Orientation in Drosophila

• Pk:Sple ratio determines orientation of the Fz asymmetry relative to Ds/Fj gradients
• Ratio of Pk and Sple is strikingly different in the eye versus the wing
• Pk and Sple have antagonistic functions and form different complexes
• Sple-Dachs cooperation polarizes Sple at the cell edge with the highest Ds level

SummaryIn Drosophila, planar cell polarity (PCP) molecules such as Dachsous (Ds) may function as global directional cues directing the asymmetrical localization of PCP core proteins such as Frizzled (Fz). However, the relationship between Ds asymmetry and Fz localization in the eye is opposite to that in the wing, thereby causing controversy regarding how these two systems are connected. Here, we show that this relationship is determined by the ratio of two Prickle (Pk) isoforms, Pk and Spiny-legs (Sple). Pk and Sple form different complexes with distinct subcellular localizations. When the amount of Sple is increased in the wing, Sple induces a reversal of PCP using the Ds-Ft system. A mathematical model demonstrates that Sple is the key regulator connecting Ds and the core proteins. Our model explains the previously noted discrepancies in terms of the differing relative amounts of Sple in the eye and wing.

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