Regulation of PCP by the Fat signaling pathway

Abstract

Planar cell polarity (PCP) in epithelia, orthogonal to the apical-basal axis, is essential for numerous developmental events and physiological functions. Drosophila model systems have been at the forefront of studies revealing insights into mechanisms regulating PCP and have revealed distinct signaling modules. One of these, involving the atypical cadherins Fat and Dachsous and the ectokinase Four-jointed, appears to link the direction of cell polarization to the tissue axes. We discuss models for the function of this signaling module as well as several unanswered questions that may guide future investigations.

Keywords: Fat; intercellular signaling; planar cell polarity.

Figure 1.

PCP in the Drosophila wing epithelium. Global directional cues, encoded by expression gradients or diffusion of secreted factors, provide directional information. The core module coordinates and amplifies polarity by intercellular communication and feedback mechanisms, localizing distinct protein complexes to opposite sides of the cell. Cells respond with appropriate tissue-specific behaviors. In the wing (and much of the adult cuticle), each cell produces a prehair from the distal side of the cell that points distally. Examples of wings showing polarity in wild type, a core mutant (dsh¹), and a Ft/Ds/Fj module mutant (ft).

Figure 2.

Schematics of polarization mechanisms in the wing, eye, and abdomen. Gradients of Fj and Ds in each tissue or compartment provide directional information. Core proteins (Fmi, Fz, Dsh, Dgo, Vang, and Pk) segregate to opposite sides of the cell. Ft/Ds/Fj-dependent MTs may provide directional information to orient this segregation. In the eye, asymmetric core proteins bias Notch–Delta signaling between the R3 and R4 precursors, leading to dorsal and ventral polarity of ommatidia in the respective halves of the eye. In the abdomen, gradients of Ds and Fj are oppositely oriented in anterior and posterior compartments. Localization of core components is presumed based on hair polarity.

Figure 3.

Cartoons of Fat, Dachsous, and truncated Fat derivatives. Conserved extracellular domains are indicated. Sites of phosphorylation by Fj are marked with “P,” and cleavage sites are marked with arrows. Known intracellular binding sites are shown, as are putative functional domains identified by various structure/function studies. FtΔECDΔN-1 and FtΔECDΔ1-C were constructed by Matakatsu and Blair (2012).