Frizzled-7 modulates Goblet and Paneth cell fate and maintains the homeostasis in intestines.

Intestinal homeostasis depends on the interactions among the intestinal epithelium, the immune system, and the microbiota. Because of these complicated connections, there are many problems that need to be solved. Current research has indicated that the target genes under Wnt signaling are responsible for controlling intestinal stem cell fate and modulating intestinal homeostasis. As our data shown, loss of Frizzled-7 (Fzd7), an important element in the Wnt signaling, interrupted the differentiation of intestinal stem cells into absorptive progenitors instead of secretory progenitors (precursors of goblet and Paneth cells). The alteration in canonical Wnt and Notch signaling pathways interrupted the epithelial homeostasis resulting to a decrease of physical protection in intestines. Several phenotypes in Fzd7-deleted model were similar to the features of enterocolitis, such as shortened intestines, decreased numbers of goblet cells and Paneth cells, and severe inflammation. Additionally, loss of Fzd7 exacerbated the defects in a chemical-induced colitis model and could initiate tumorigenesis. These findings may provide important information for the discovery of efficient therapeutic methods to treat enterocolitis and related cancers in the intestines.