During the development of the small intestine, a smooth-surfaced endodermal tube is remodelled to form finger-like projections (villi), where food absorption occurs, and flask-shaped invaginations (crypts), which contain the intestinal stem cells. On p. , Madison and colleagues report that a combined sonic (Shh) and Indian (Ihh) hedgehog signal produced by the epithelial cells in the developing intestine controls villus formation and patterning in a paracrine manner. By generating transgenic mice that express hedgehog (Hh) interacting protein – a pan-Hh inhibitor– in the neonatal intestine, the researchers show that even weak inhibition of Hh signalling perturbs crypt/villus patterning, causing the mislocalisation of subepithelial myofibroblasts to the villus tips and increased epithelial proliferation. Overall, conclude the researchers, the intestinal epithelium normally patterns the crypt-villus axis by sending Hh signals to underlying subepithelial myofibroblasts, the likely producers of the Wnt signals that control epithelial proliferation.
