Asymmetric homotypic interactions of the atypical cadherin Flamingo mediate intercellular planar cell polarity signaling in Drosophila melanogaster

Acquisition of planar cell polarity (PCP) in epithelia involves intercellular communication, during which cells align their polarity with that of their neighbors. The transmembrane proteins Frizzled and Van Gogh are essential components of the intercellular communication mechanism, as loss of either strongly perturbs the polarity of neighboring cells. However, how Frizzled and Van Gogh communicate polarity information across cell boundaries is poorly understood. The atypical cadherin, Flamingo, has been implicated in this process, yet whether Flamingo acts permissively as a scaffold, or instructively as a signal is unclear. Here, we provide evidence that Flamingo functions instructively to mediate Fz-Vang intercellular signal relay, recruiting Frizzled and Van Gogh to opposite sides of cell boundaries. We propose that two functional forms of Flamingo form homodimers that signal bidirectionally and function asymmetrically, instructing unequal responses in adjacent cell membranes to establish molecular asymmetry.