Signaling through fibroblast growth factor receptor 2b plays a key role in the development of the exocrine pancreas
- *Institut National de la Santé et de la Recherche Médicale U457, Hospital R. Debré, 48, Boulevard Sérurier, 75019 Paris, France; and ‡Department of Genetic Biochemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501, Japan
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Edited by Donald F. Steiner, The University of Chicago, Chicago, IL, and approved March 30, 1999 (received for review December 16, 1998)
Abstract
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.
Footnotes
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↵ † To whom reprint requests should be addressed. e-mail: scharfma{at}infobiogen.fr.
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This paper was submitted directly (Track II) to the Proceedings Office.
- ABBREVIATIONS:
- FGF,
- fibroblast growth factor;
- FGFR,
- fibroblast growth factor receptor;
- E(n),
- embryonic day
- Copyright © 1999, The National Academy of Sciences
