Signaling through fibroblast growth factor receptor 2b plays a key role in the development of the exocrine pancreas.
The development of the pancreas depends on epithelial-mesenchymal interactions. Fibroblast growth factors (FGFs) and their receptors (FGFRs 1-4) have been identified as mediators of epithelial-mesenchymal interactions in different organs. We show here that FGFR-2 IIIb and its ligands FGF-1, FGF-7, and FGF-10 are expressed throughout pancreatic development. We also show that in mesenchyme-free cultures of embryonic pancreatic epithelium FGF-1, FGF-7, and FGF-10 stimulate the growth, morphogenesis, and cytodifferentiation of the exocrine cells of the pancreas. The role of FGFs signaling through FGFR-2 IIIb was further investigated by inhibiting FGFR-2 IIIb signaling in organocultures of pancreatic explants (epithelium + mesenchyme) by using either antisense FGFR-2 IIIb oligonucleotides or a soluble recombinant FGFR-2 IIIb protein. Abrogation of FGFR-2 IIIb signaling resulted in a considerable reduction in the size of the explants and in a 2-fold reduction of the development of the exocrine cells. These results demonstrate that FGFs signaling through FGFR-2 IIIb play an important role in the development of the exocrine pancreas.
Miralles
F
F
Institut National de la Santé et de la Recherche Médicale U457, Hospital R. Debré, 48, Boulevard Sérurier, 75019 Paris, France.
Czernichow
P
P
Ozaki
K
K
Itoh
N
N
Scharfmann
R
R
D000818:Animals; D018076:DNA, Complementary; D004622:Embryo, Mammalian; D005314:Embryonic and Fetal Development / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016220:Fibroblast Growth Factor 1; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000494:pharmacology; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006133:Growth Substances / Q000235:genetics / Q000494:pharmacology; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009924:Organ Culture Techniques; D010179:Pancreas / Q000166:cytology / Q000196:embryology*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D018076:DNA, Complementary; C496464:Fgf10 protein, mouse; C496465:Fgf10 protein, rat; C496454:Fgf7 protein, mouse; C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D016376:Oligonucleotides, Antisense; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; C496354:Fgfr2 protein, mouse; C496356:Fgfr2 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2