Stomach development is dependent on fibroblast growth factor 10/fibroblast growth factor receptor 2b-mediated signaling.
OBJECTIVE
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.
Spencer-Dene
Bradley
B
Experimental Pathology Laboratory, Cancer Research UK, London Research Institute, London, England. b.spencer-dene@imperial.ac.uk
Sala
Frederic G
FG
Bellusci
Saverio
S
Gschmeissner
Stephen
S
Stamp
Gordon
G
Dickson
Clive
C
D000818:Animals; D019521:Body Patterning / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development / Q000502:physiology; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism*; D005753:Gastric Mucosa / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D010295:Parietal Cells, Gastric / Q000166:cytology; D011708:Pylorus / Q000196:embryology; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013270:Stomach / Q000196:embryology*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism
D051526:Fibroblast Growth Factor 10; D014157:Transcription Factors; D051497:Receptor, Fibroblast Growth Factor, Type 2