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


CONCLUSIONS
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.
van den Brink
G R
GR
Department of Experimental Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands. g.r.vandenbrink@amc.uva.nl
Hardwick
J C H
JC
Nielsen
C
C
Xu
C
C
ten Kate
F J
FJ
Glickman
J
J
van Deventer
S J H
SJ
Roberts
D J
DJ
Peppelenbosch
M P
MP
D000328:Adult; D002454:Cell Differentiation; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005748:Gastric Fundus / Q000737:chemistry* / Q000166:cytology; D053823:Hedgehog Proteins; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D008467:Meckel Diverticulum / Q000378:metabolism*; D008679:Metaplasia; D012333:RNA, Messenger / Q000032:analysis*; D015534:Trans-Activators / Q000032:analysis* / Q000235:genetics
D053823:Hedgehog Proteins; D012333:RNA, Messenger; C509239:SHH protein, human; D015534:Trans-Activators