Figure 6. Model demonstrating threshold of Smo accumulation to PC necessary for priming effect.

Cyclopamine induces ciliary Smo localization to a threshold necessary for priming activity to occur as observed in NIH-3T3 cells (A). In cell lines such as HEPM or C3H10T1/2, cyclopamine does not induce ciliary Smo localization to this threshold level (B). Upon cyclopamine withdrawal, followed by Shh addition, hyper-responsiveness as measured by Gli1 up-regulation is only observed in NIH-3T3 cells (C) and not cell lines where the required level of ciliary Smo accumulation was not achieved by cyclopamine pre-treatment (D).