The Hedgehog family of ligands was originally identified in mutagenesis screens of Drosophila embryos. Hedgehog signaling in multiple tissues is important during embryonic development. A common theme regarding Hedgehog expression in adult tissues is that tissue injury reactivates the developmental pattern of expression. In most instances, this appears to be important to initiate tissue repair. In the gastrointestinal (GI) tract, where epithelial cells are constantly replenished from progenitor populations, Hedgehog signaling also appears to be essential for regeneration. By contrast, reactivated Hedgehog signaling in adult tissues does not automatically predispose the tissue to transformation, but instead requires sustained tissue injury in the form of chronic inflammation. In this chapter, we review what is known about Hedgehog ligands and signaling during development of relevant organs, and discuss how the patterns of Hedgehog regulation are recapitulated in the GI tract during embryogenesis, adult homeostasis, and neoplastic transformation.
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