Tuning of Network Parameters Predicts Tissue-Specific Cooperation between Su(dx) and Dx to Downregulate Notch
(A and B) Modeling of the combined loss of function of Su(dx) and dx on N signaling ([NICD] arbitrary units) when lysosomal activation component is reduced (A) or increased (B). These models differ from that shown in Figure 5B only by a 5-fold reduction (A) or 5-fold increase (B) in k9, which determines lysosomal activation component. Black dot represents WT [Dx] and [Su(dx)], color shading is as described in the legend for Figure 5B.
(C–E) Su(dx), dx mutant combination results in N gain of function. (C) WT leg, tarsal joints between segments T2/T3, and T3/T4 indicated. (D) Extra joint tissue (arrowhead) observed in dx;Su(dx). (E) Percent legs with ectopic joint increases with temperature in double mutants (p < 0.01, Fisher’s exact test, n > 60 legs per genotype).
(F) Additional copy of WT Su(dx) in dx mutant results in loss of joints at 25°C (86.4% legs, n = 66) not seen with additional WT Su(dx) copy in WT background (n = 80).
(G) Dx expression in WT results in both partial joint loss (asterisk) and ectopic joint material (arrowhead).
(H) When active Rab7 (Rab7QL) is coexpressed with Dx, joint tissue is lost (arrow).
(I) TRPML coexpression with Dx results in loss of joints.
(J and K) Coexpression of TRPML with Dx increases wingless expression in wing discs compared to Dx alone (arrow). TRPML expression alone has no effect (data not shown).
See also Data File S1.