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PMID:16247775

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Citation

Kim, JH, Huang, Z and Mo, R (2005) Gli3 null mice display glandular overgrowth of the developing stomach. Dev. Dyn. 234:984-91

Abstract

The role of the Hedgehog signaling pathway in various aspects of gut development is still poorly understood. In the developing stomach, Sonic (Shh) and Indian (Ihh) hedgehog are expressed in both distinct and overlapping regions. Loss of Sonic hedgehog function in the stomach results in a glandular phenotype of intestinal transformation and overgrowth. These changes are reminiscent of the pre-malignant lesion, intestinal metaplasia. To determine the role of Hedgehog-related transcription factors, Gli2 and Gli3, in Shh signaling during stomach development, we conducted a mutant analysis of glandular stomach from Shh, Gli2, and Gli3 mutant mice. Although Gli2 principally mediates the activator function of Shh, surprisingly we observed minimal changes in glandular development in the Gli2 mutant stomach. Furthermore, Gli3, which typically functions as a repressor of Hedgehog signal, showed a striking phenocopy of the glandular expansion and intestinal transformation found in Shh mutant stomach. A reduction in apoptotic events was seen in all mutant stomachs with no appreciable changes in proliferation. Both Shh and Gli3 mutant stomachs displayed early changes of intestinal transformation but these did not impact on the overall differentiation of the gastric epithelium. Interestingly, the observation that Gli3 shares a similar glandular phenotype to Shh mutant stomach reveals a possible novel role of Gli3 activator in the developing stomach. The embryonic stomach is a unique model of the Hedgehog pathway function and one that may help to uncover some of the mechanisms underlying the development of intestinal metaplasia.

Links

PubMed Online version:10.1002/dvdy.20542

Keywords

Animals; Apoptosis/physiology; Gastric Mucosa/embryology; Gastric Mucosa/metabolism; Gastric Mucosa/pathology; Gastric Mucosa/ultrastructure; Hedgehog Proteins; Immunohistochemistry; In Situ Hybridization; In Situ Nick-End Labeling; Kruppel-Like Transcription Factors/genetics; Kruppel-Like Transcription Factors/metabolism; Metaplasia/genetics; Metaplasia/metabolism; Mice; Mice, Mutant Strains; Microscopy, Electron, Transmission; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Signal Transduction/genetics; Signal Transduction/physiology; Trans-Activators/genetics; Trans-Activators/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:GLI3

acts_upstream_of_or_within

GO:0048754: branching morphogenesis of an epithelial tube

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856276

P

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0048557: embryonic digestive tract morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856276

P

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0048754: branching morphogenesis of an epithelial tube

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856276

P

has_participant:(EMAPA:17625)

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0048557: embryonic digestive tract morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856276

P

has_participant:(EMAPA:17623)

Seeded From UniProt

complete


See also

References

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