(A) Protein model of the intracellular domain of Fat showing the transmembrane domain (TM), regions conserved with mammalian Fat4 (blue, A–F) (defined by Pan et al., 2013), regions associated with the major growth suppressive function of Fat (red) (HM, Bossuyt et al., 2013; Hippo-N, Hippo-C, Matakatsu and Blair, 2012; H2, Zhao et al., 2013), region required for Dco binding (green) (Sopko et al., 2009), mutV region (orange) (Pan et al., 2013), Su(DN) region (purple) (Matakatsu and Blair, 2012), and two point mutations, ftsum (Bossuyt et al., 2013) and ft61 (this study). Size and position of regions are drawn to scale relative to the ICD. (B–C) Mosaic adult eye assay. Heterozygous wild-type cells have red pigment and homozygous mutant cells lack pigment. Compared to (B) control FRT40A mosaic eyes, (C) ft61 mosaic eyes are larger and have more mutant tissue. (D) ftGrv/ft8; ft+ adult wing and (D′–D‴) confocal slice of a wing disc showing that Fbxl7 (red) is localized to the apical membrane similar to E-cad (green). (E) ftGrv/ft8; ftΔD adult wing and (E′–E‴) confocal slice showing that Fbxl7 (red) apical localization is disrupted. (F) ftGrv/ft8; ftΔF adult wing and (F′–F‴) confocal slice showing that Fbxl7 (red) apical localization is normal and similar to that in D′–D‴. (G) Confocal slice of a disc containing a MARCM ft61 clone (green) and stained for Fbxl7 (red) and E-cad (blue). Fbxl7 apical localization is normal in ft61 cells (H) Co-immunoprecipitation experiment in S2 cells. Fat-V5, Fat61-V5, and FatΔF-V5 pull down with FLAG-Fbxl7, whereas pull down of FatΔD-V5 and FatmutV-V5 is reduced. Expressed Fat proteins contain only transmembrane and cytoplasmic regions (ICD). (I–M) Wing imaginal discs (and associated leg and haltere discs) at low magnification. Compared to (I) control tub-Gal4 discs, (J) ftGrv/ft8 and (K) ft61/ft8 discs are larger and have more folds. (L) Ubiquitous expression of Fbxl7 does not rescue ftGrv/ft8 disc overgrowth. (M) Ubiquitous expression of Fbxl7 rescues disc overgrowth of ft61/ft8. (N–O) Adult wing from (N) control tub-Gal4 and (O) ubiquitous expression of FLAG-Fbxl7 in an ft61/ft8 background. Animal lethality is rescued. (P–Q′) Confocal slice through the eye imaginal disc showing MARCM clones (green) and anti-Diap1 staining (red). (P–P′) dco3 clones have elevated Diap1 levels and are overgrown, whereas (Q–Q′) dco3 clones expressing FLAG-Fbxl7 have wild-type Diap1 levels and are reduced in size.