Hedgehog Signaling in Intestinal Development and Homeostasis

The hedgehog (Hh) signaling pathway plays several diverse regulatory and patterning roles during organogenesis of the intestine and in the regulation of adult intestinal homeostasis. In the embryo, fetus, and adult, intestinal Hh signaling is paracrine: Hh ligands are expressed in the endodermally derived epithelium, while signal transduction is confined to the mesenchymal compartment, where at least a dozen distinct cell types are capable of responding to Hh signals. Epithelial Hh ligands not only regulate a variety of mesenchymal cell behaviors, but they also direct these mesenchymal cells to secrete additional soluble factors (e.g., Wnts, Bmps, inflammatory mediators) that feed back to regulate the epithelial cells themselves. Evolutionary conservation of the core Hh signaling pathway, as well as conservation of epithelial/mesenchymal cross talk in the intestine, has meant that work in many diverse model systems has contributed to our current understanding of the role of this pathway in intestinal organogenesis, which is reviewed here.

Automated summary

The Hedgehog (Hh) signaling pathway plays crucial regulatory and patterning roles during intestine organogenesis and homeostasis in adults, with Hh ligands expressed in the endodermally derived epithelium and signal transduction confined to the mesenchymal compartment. This leads to a feedback loop where epithelial Hh ligands regulate mesenchymal cell behaviors and guide them to secrete additional soluble factors that in turn regulate epithelial cells. The evolutionary conservation of this pathway and epithelial/mesenchymal crosstalk in the intestine has contributed to our understanding of its role in intestinal organogenesis.