Unexpected Hedgehog–Wnt interactions in epithelial differentiation

Wnt and Hedgehog (Hh) signalling regulate stem-cell self-renewal and differentiation in a range of epithelia and the inappropriate activation of these pathways contributes to epithelial cancers. Recently, it was reported that Indian Hedgehog (Ihh) antagonises Wnt signalling in colonic epithelium. This observation contrasts with other reports of positive synergy between the pathways and challenges the view that systemically administered Hedgehog antagonists could be beneficial for the treatment of intestinal tumours. The work is discussed in the broader context of Ihh expression and function in epithelia and the different ways in which the Hh and Wnt pathways interact.