Sonic hedgehog expression correlates with fundic gland differentiation in the adult gastrointestinal tract

Abstract

Background: Sonic hedgehog (Shh) is an important endodermal morphogenetic signal during the development of the vertebrate gut. It controls gastrointestinal patterning in general, and gastric gland formation in particular. We have previously shown that Shh regulates gastric gland proliferation in the adult but detailed analysis of its expression along the adult gastrointestinal tract has never been undertaken. We therefore studied Shh expression along the normal human and rodent adult gastrointestinal tract as well as in intestinal metaplasia of the stomach, gastric and intestinal metaplasia of the oesophagus, and gastric heterotopia in Meckel's diverticulum. Methods: The studies were performed with in situ hybridisation and by immunohistochemistry using an antibody that recognises the Shh precursor form. Results: We found that in the normal gastrointestinal tract, high levels of Shh were expressed in the fundic glands of the stomach. Shh expression was also found in fundic gland metaplasia and heterotopia. However, Shh expression was lost in intestinal metaplasia of the stomach. Conclusion: We found a strong correlation between Shh expression and fundic gland differentiation. Our current study therefore provides evidence that in addition to its role in gastric epithelial development, Shh plays a unique role in gastric epithelial differentiation in adults.

Hedgehog signalling in colorectal tumour cells: Induction of apoptosis with cyclopamine treatment

“…2,4 Studies have shown that Hh signalling from the epithelium is required for the correct specification and patterning of the underlying mesenchyme. [5][6][7] In the adult human colon, expression of Shh mRNA has been demonstrated in a few epithelial cells at the base of normal intestinal crypts, 8 suggesting a role for SHH in the maintenance of the stem cell compartment. Further evidence of a role for Hh signalling in intestinal epithelial cell proliferation comes from targeted disruption of Ihh in the mouse.…”

“…[5][6][7] A study in the adult human gut showed expression of SHH primarily in the fundic glands of the stomach. 8 Shh mRNA was detected in a small number of epithelial cells at the base of the crypts of the small and large intestine. 8 Secreted SHH and IHH signal through binding to the PTCH receptor, which, in the absence of ligand, represses the activity of the transmembrane protein SMO.…”

“…8 Shh mRNA was detected in a small number of epithelial cells at the base of the crypts of the small and large intestine. 8 Secreted SHH and IHH signal through binding to the PTCH receptor, which, in the absence of ligand, represses the activity of the transmembrane protein SMO. Release of this repression of SMO allows activation of downstream targets through the Gli transcriptional effectors (Gli1-3, mammalian homologues of the Drosophila gene Cubitus interruptus).…”

“…Although Shh expression has been reported to be coincident with the stem cell compartment in the adult colonic crypt, 8 previous studies have failed to show activating mutations of Shh, or Abbreviations: APC, adenomatous polyposis coli; BCC, basal cell carcinoma; dpc, days postcoitum; Hh, Hedgehog; IHH, Indian hedgehog; PARP, poly(ADP-ribose) polymerase; PTCH, patched; SHH, Sonic hedgehog; SMO, smoothened; Tcf, T-cell factor; TGF, transforming growth factor.…”

Shh/BMP‐4 signaling pathway is essential for intestinal epithelial development during Xenopus larval‐to‐adult remodeling

“…Also in the human adult intestine, Shh expression is restricted to the region corresponding to stem cells (van den Brink et al, 2002;de Santa Barbara et al, 2003) and upregulated in the neoplastic or inflammatory intestine when the stem cells compensate for the epithelial damage (Berman et al, 2003;Nielsen et al, 2004). Therefore, it seems likely that the stem cells may make their niche adequate for the new epithelial formation by expressing Shh, which in turn ) and Chordin proteins to the medium changes the proliferating activity of intestinal tissues cultured for 5 days.…”