The Hedgehog (Hh) genes play a key role in the regulation of embryonic development and govern processes such as cell differentiation, cell proliferation, and tissue patterning. In vertebrate embryos, Hh gene expression regulates correct formation of limbs, skeleton, muscles, and organs including stomach. In the adult, the Hh pathway functions in tissue repair and regeneration, along with maintenance of stem cells. Sonic Hedgehog (Shh) signaling has been extensively studied for its role in developmental and cancer biology. Recent advances in the field of gastroenterology show that in the stomach, Shh is responsible for proper differentiation of the gastric glands. The aberrant activity of the Shh signaling pathway leads to an altered gastric differentiation program and loss of gastric acid secretion that is the predominant function of the stomach. In this chapter, we review the most recent findings that reveal the role of Shh as a regulator of gastric function and differentiation and how this signaling is dysregulated during the development of gastric cancer in response bacterial infection.
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