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. 2014 Mar 27;10(3):e1003507. doi: 10.1371/journal.pcbi.1003507

Figure 5. Morphogen knockout/inhibition simulations.

Figure 5

Panel A displays average crypt and villus GEC populations in SEGMEnT when exposed to Wingless-related integration site (Wnt) inhibition. Panels B–D displays three frames from a SEGMEnT simulation of Wnt inhibition. Panel B represents baseline homeostasis prior to Wnt application. Panel C was captured at t = 1755 min, shortly after Wnt application. Cells then quickly differentiate as the β-catenin destruction complex is activated; the increased Hh signal from the newly differentiated cells combined with the Wnt inhibitor quickly eliminate all Wnt activity. Panel D was captured at t = 2160 min, at which point with the elimination of Wnt, the crypt no longer exists, there are few proliferating cells, and the villi have lost significant cellularity. Panel E displays average crypt and villus GEC populations in SEGMEnT when exposed to Sonic Hedgehog Homolog (Hh) inhibition. Panel F represents the system at baseline homeostasis prior the application of Hh inhibition. Panel G was captured at 5010 min, shortly after application of Hh inhibition. After application of the Hh inhibitor, the crypt expands rapidly. Initially, there is slight villus shrinkage as differentiation is temporarily halted by the now uninhibited Wingless-related integration site (Wnt) gradient. Panel H was captured at t = 6000 min. As the system adjusts to the lack of Hh, homeostasis is reached and persistent crypt hyperplasia exists throughout the system (Panel H).