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. 2014 May 22;157(5):1160–1174. doi: 10.1016/j.cell.2014.03.050

Figure 5.

Figure 5

Modeling Consequences of Su(dx) and dx Mutations on Notch Signaling in the Drosophila Wing

(A) N endocytic trafficking routes. Asterisks mark experimentally observed temperature-dependent steps. Key fluxes are designated r.

(B) Model of the effects of mutations of Su(dx) and dx on N signaling ([NICD] arbitrary units) in the Drosophila wing at 29°C. Arrowhead marks mutual suppression observed in double mutants. Black dot represents WT concentrations of both Dx and Su(dx). Asterisk marks stronger loss of Notch signaling expected from increased Su(dx) in the absence of Dx. Yellow shading indicates expected WT conditions, orange to red shading indicates increased expectation of a Notch gain of function phenotype (wing vein gaps) and green to blue shading indicates increased likelihood of a Notch loss of function phenotype (vein thickening).

(C–F) Mutual suppression resulting from combined Su(dx) and dx mutations restores temperature-sensitive phenotypes of each back to WT at 29°C.

(G) Increasing WT Su(dx) copy number enhances the dx mutant wing phenotype.

(H) Su(dx) mutant wing phenotype is suppressed by car.

(I) Simulation of N signaling (NICD) versus temperature in WT and mutant backgrounds. Arrowheads mark expected upper and lower signaling thresholds corresponding to yellow shaded area in (B).

(J) dx mutant phenotype weakens as temperatures decrease from 25°C down to 16°C but worsen again at 14°C. At 25°C, Su(dx) mutants suppress dx phenotype, but as temperature is lowered, the loss of Su(dx) has less effect on the strength of the dx phenotype. At 18°C and below, Su(dx) mutation enhances dx phenotype. Arrowheads indicate distal thickening on L3 and L4 veins.

(K) Percent wings with L3 and L4 vein thickening. The dx phenotype was increased at 14°C compared to 16°C (p < 0.05) and reduced at 18°C compared to 25°C (p < 0.001). Enhancement or suppression of dx phenotype in dx;Su(dx) double mutant flies was observed at different temperatures (p < 0.0001, Fisher’s exact test, n > 40 for each genotype tested).

See also Data File S1.