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Updated: Jan 10, 2026
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Stomach development is dependent on fibroblast growth factor 10/fibroblast growth factor receptor 2b-mediated
Bradley Spencer-Dene1, Frederic G Sala, Saverio Bellusci
1Experimental Pathology Laboratory, Cancer Research UK, London Research Institute, London, England. b.spencer-dene@imperial.ac.uk
Background & Aims:
Fibroblast growth factors (Fgfs) and their receptors (Fgfrs) are important intercellular signaling molecules that are essential to mammalian embryonic development. The signaling pathways between endoderm-derived gastric epithelium and the surrounding mesenchyme are largely unknown; however, the developmental expression profile of the IIIb isoform of Fgfr2 (Fgfr2b) and its main ligand, Fgf10, suggest that they may be strong candidates. Mice lacking either component (Fgfr2b-/- or Fgf10-/-) were examined to determine the role of Fgfr2b-mediated signaling during gastric organogenesis.
Methods:
Stomachs from embryonic day 13.5-18.5 Fgfr2b-/-, Fgf10-/-, and wild-type littermates were collected and analyzed by conventional histology, immunohistochemistry, in situ hybridization, and electron microscopy.
Results:
Fgfr2b-/- and Fgf10-/- fetuses had stomachs smaller than wild-type, consisting of relatively proportionate forestomach but disproportionately reduced glandular stomach, the mucosa of which has low cytoarchitectural complexity with a spiral arrangement of large mucosal folds. During mid to late fetal stages (embryonic day 15.5-18.5), epithelial differentiation to mucous and chief cell lineages was rudimentary, with no expression of several early cytodifferentiation markers including GATA4, GATA6, and H+/K+-adenosine triphosphatase and abnormal expression of members of the hedgehog family of signaling molecules.
Conclusions:
Fgfr2b and Fgf10 are part of a signaling network with Sonic hedgehog and Indian hedgehog that are essential to anterior-posterior and radial patterning in gastric development.
Insights
Fibroblast Growth Factor Receptor 2b (Fgfr2b) and Fibroblast Growth Factor 10 (Fgf10) are crucial for gastric development. Their absence leads to smaller stomachs with impaired glandular development and abnormal cell differentiation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Gastroenterology
Background:
- Fibroblast growth factors (Fgfs) and their receptors (Fgfrs) are key intercellular signaling molecules in mammalian embryonic development.
- Signaling pathways between gastric epithelium and mesenchyme are not well understood.
- Fgfr2b and Fgf10 are implicated in gastric organogenesis due to their expression patterns.
Purpose of the Study:
- To investigate the role of Fgfr2b-mediated signaling in gastric organogenesis.
- To determine the function of Fgf10 in the developing stomach.
- To elucidate the signaling network governing gastric development.
Main Methods:
- Analysis of stomachs from Fgfr2b-/- and Fgf10-/- mouse models.
- Utilized histology, immunohistochemistry, in situ hybridization, and electron microscopy.
- Examined developmental stages from embryonic day 13.5 to 18.5.
Main Results:
- Fgfr2b-/- and Fgf10-/- fetuses exhibited smaller stomachs with disproportionately reduced glandular regions.
- Mucosal cytoarchitecture was simplified with abnormal fold arrangement.
- Epithelial differentiation was rudimentary, with aberrant expression of cytodifferentiation markers and hedgehog signaling molecules.
Conclusions:
- Fgfr2b and Fgf10 are essential for anterior-posterior and radial patterning in gastric development.
- These factors are integral to a signaling network involving Sonic hedgehog and Indian hedgehog.
- Disruption of this pathway severely impacts gastric organogenesis and differentiation.
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