EGF receptor/Rolled MAP kinase signalling protects cells against activated Armadillo in the Drosophila eye

Abstract

β-catenin/Armadillo are transcriptional co-activators that mediate Wnt signalling in normal development. Activated forms of β-catenin are oncogenic. We have constructed mutant forms of Drosophila Armadillo which correspond to common human oncogenic mutations, and find them to activate Armadillo constitutively. When expressed in the Drosophila eye, these eventually induce apoptosis in all cell types. Intriguingly, cells in the eye are resistant to the effects of activated Armadillo for a long period prior to the onset of cell death at the mid-pupal stage. This latency is conferred by EGF receptor (EGFR)/MAP kinase signalling, which prevents activated Armadillo from inducing apoptosis; when EGFR signalling naturally ceases, the cells rapidly die. Nemo, the Drosophila homologue of NLK in mice and LIT-1 in Caenorhabditis elegans, does not antagonize activated Armadillo, suggesting that the Nemo-like MAP kinases may not generally interact with Armadillo/β-catenin. Thus, our results show that activated Armadillo is subject to a specific negative control by EGFR/Rolled MAP kinase signalling.

Wingless eliminates ommatidia from the edge of the developing eye through activation of apoptosis

“…In addition, expression of an activated form of Arm results in a similar phenotype (Ahmed et al, 1998;Freeman and Bienz, 2001). We found that R cell apoptosis in apc1 mutants occurred at the same time as the perimeter cell death in wild type, with TUNEL-positive cells arising around 35 hours APF (data not shown) and peaking at 42 hours APF (Fig.…”

Wnt/β-Catenin and Estrogen Signaling Converge in Vivo

“…Genetic Interaction between ER␣ and ␤-Catenin-Constitutive activation of Armadillo in the Drosophila eye disc has been shown to induce apoptosis and consequent degeneration in the adult eye (26,27). Potentiation of ␤-catenin transcriptional activity by ER␣ in SW480 cells (Fig.…”

“…3A). Activated Armadillo has a mild apoptotic effect in the third instar larva eye disc, reportedly due to the protective counteraction at this stage by the EGFR/MAPK signaling (27). This allowed us to detect differences in apoptosis patterns in transgenic fly eye discs at this developmental stage that would otherwise be difficult to distinguish due to the onset of massive cell death at the later stages.…”

C-terminal-binding protein directly activates and represses Wnt transcriptional targets in Drosophila

“…Both inserts drive the expression of CtBP in a Gal4-dependent manner, as judged by immunostaining (see Supplementary data, Supplementary Figure S1 and data not shown). CtBP expression also strongly suppressed the effects of an activated form of Arm (Arm*; Figure 1D-F), which cannot be phosphorylated by the Axin/APC/GSK3/CKI degradation complex (Freeman and Bienz, 2001). The effect of CtBP was specific for Wnt signaling, as P[GSV] A396 and P[GSV] A132 did not suppress the small eye phenotype generated by GMR-hid, a potent activator of apoptosis (data not shown).…”