Figure 3
From: Systems biology by the rules: hybrid intelligent systems for pathway modeling and discovery
a. A feedforward motif in the hedgehog pathway is highlighted. b. To isolate the dynamics of the feedforward motif, the transforming event was made constitutively "on" and the Gli1 feedback loop to Ptc1 was deleted. A short, half-day upregulation of Shh was given at the start of day 1, then turned off. Though NmycP responded quickly to this transient signal, it was not sufficient to activate Gli1 transcription. Shh was upregulated for a longer period starting on day 4. After a one day delay, Gli1 transcription commences. Tumor growth begins when Gli1 reaches a moderately high level. When Shh transcription ends, NmycP levels begin to drop immediately, but Gli1 decline is delayed. Thus, a series of prolonged aberrant Shh activation events could sustain tumor growth.