Su(fu) switches Rdx functions to fine-tune hedgehog signaling in the Drosophila wing disk

Hedgehog (Hh) signaling plays a central role in pattern formation by regulating transcription factor Cubitus interruptus (Ci). Previously, Roadkill (Rdx, also called HIB) was shown to inhibit Ci activity by two distinct mechanisms, depending on the Hh 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 Hh signal, Rdx blocks the nuclear entry of Ci-155. In contrast, in the region farther from the A/P boundary, where cells receive moderate levels of Hh, Rdx induces Ci-155 degradation in the nucleus. Here, we report that Suppressor of fused, Su(fu), causes the Rdx switch between mechanisms. A strong Hh signal induces rdx expression and suppresses su(fu) expression, whereas moderate levels of Hh induce moderate levels of rdx expression and high levels of su(fu) expression. Rdx blocks entry of Ci-155 into the nucleus in the absence of Su(fu) and Rdx induces the degradation of Ci-155 in the nucleus in the presence of a threshold level of Su(fu). Thus, the Su(fu)-induced switch between the dual actions of Rdx in response to the Hh signal strength plays a role in fine-tuning Hh signaling.