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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

Gastroenterology
|April 19, 2006
PubMed
Abstract

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.