Fig. 2.

Differentiation of intestinal epithelial cells to absorptive and secretory lineages and effects of Notch and Wnt. Lgr5-positive pluripotent stem cells cycle in the crypt base under the influence of both Notch and Wnt. If levels of Notch signaling are high, committed progeny are directed towards differentiation along the absorptive pathway, ultimately resulting in mature enterocytes that express (among other markers) the chloride-bicarbonate exchanger downregulated in adenoma (DRA). Notch also suppresses the effect of Wnt that otherwise downregulates absorptive differentiation. On the other hand, when Notch signaling is relatively less active, absorptive differentiation is suppressed by unopposed Wnt activity, and differentiation to the various secretory lineages directed by Atoh1 expression, goblet cells expressing mucin 2 (Muc2), Paneth cells expressing defensing 5 (Def5), enteroendocrine cells expressing chromogranin A (CgA) and tuft cells, is promoted (44).