The importance of Wnt signalling in intestinal homeostasis has been well described. However, distinguishing roles for different sources of Wnt, from either the epithelium or the stromal cells of the intestine, has been harder to dissect. Now, Nan Gao and colleagues identify two uncharacterised populations of Wnt-producing stromal cells in the mouse intestine and investigate how Wnt produced by these cells and intestinal epithelial cells contributes to colonic healing. The authors observe a reduction in the number of Reg4+ deep crypt secretory cells (analogous to Paneth cells in the small intestine) in the colons of mice depleted of epithelial Wnt. However, mice depleted of both stromal and epithelial Wnt display abnormal gland morphology in addition to defects in Reg4+ differentiation. Furthermore, they find that colonic regeneration after chemically induced injury is impaired in mice lacking Wnt production in the epithelium, but the phenotype is further exacerbated in mice lacking Wnt produced in both the epithelium and stromal cells. Together, these data indicate an additive role for different Wnt sources in maintaining colon homeostasis and in colonic recovery after injury.
