S u(fu) switches R dx functions to fine‐tune hedgehog signaling in the D rosophila wing disk

Hedgehog ( H h) signaling plays a central role in pattern formation by regulating transcription factor Cubitus interruptus ( C i). Previously, R oadkill ( R dx, also called HIB ) was shown to inhibit C i activity by two distinct mechanisms, depending on the H h signal strength (Seong et al . 2010, PLoS One 5, e15365). In the anterior region abutting the anterior/posterior ( A / P ) boundary of the wing disk, where cells receive a strong H h signal, R dx blocks the nuclear entry of C i‐155. In contrast, in the region farther from the A / P boundary, where cells receive moderate levels of H h, R dx induces C i‐155 degradation in the nucleus. Here, we report that S uppressor of fused, S u(fu), causes the R dx switch between mechanisms. A strong H h signal induces rdx expression and suppresses su(fu) expression, whereas moderate levels of H h induce moderate levels of rdx expression and high levels of su(fu ) expression. R dx blocks entry of C i‐155 into the nucleus in the absence of S u(fu) and R dx induces the degradation of C i‐155 in the nucleus in the presence of a threshold level of S u(fu). Thus, the S u(fu)‐induced switch between the dual actions of R dx in response to the H h signal strength plays a role in fine‐tuning H h signaling.