The important role of feedback loops is illustrated by isolating the Shh-to-Gli1 pathway in the hedgehog model. NmycP and the transforming event required for tumor growth are constitutively on in this simulation. a. The feedback from the transcription factor Gli1 to Ptc1 transcriptional activation is operative. As shown in b, Ptc1 transcription is maintained at an equilibrium level that is high enough to keep Gli1 below the threshold required for tumor growth. In c, the feedback is turned off; time courses in d show that increased Gli1 levels no longer influence Ptc1 expression, which is then effectively repressed by Shh. High levels of Gli1 are thus maintained and tumor growth is high. In this simulation Shh is constitutively at its highest level (0.1) and thus not shown.