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. Author manuscript; available in PMC: 2014 Dec 17.
Published in final edited form as: Gastroenterology. 2009 Nov 10;138(2):550–561.e8. doi: 10.1053/j.gastro.2009.11.002

Figure 8.

Figure 8

Proposed mechanism for the development of hyperproliferation in the surface mucous cells with loss of Shh. (A) In the epithelium, loss of Shh disrupts the inhibitory pathway between somatostatin and gastrin, thus inducing hypergastrinemia. Hypergastrinemia up-regulates the expression of Ihh within the epithelial surface mucous cells. (B) Upon binding to Ptch receptor in the mesenchyme, Ihh removes the inhibitory effect of Ptch on Smo and causes the translocation of Gli1 to the nucleus, where it induces expression of target gene Snail and canonical Wnt. (C) Activation of the Wnt pathway within the epithelium targets cyclin D1, which promotes cell proliferation.