The IIIb isoform of fibroblast growth factor receptor 2 is required for proper growth and branching of pancreatic ductal epithelium but not for differentiation of exocrine or endocrine cells.
Fibroblast growth factors (Fgfs) and their receptors have been implicated in embryonic pancreas development. Recently it was shown that Fgf10, a major ligand for the IIIb isoform of fibroblast growth factor receptor 2 (Fgfr2b), has an important regulatory role in early pancreas development. The aim of our study was to define the role of Fgfr2b in pancreas development by analyzing the phenotype of Fgfr2b (-/-) mice. Pancreases of Fgfr2b (-/-) embryos were noticeably smaller than the wild type littermates during embryogenesis, and pancreatic ductal branching as well as duct cell proliferation was significantly reduced. However, both exocrine and endocrine pancreatic differentiation occurred relatively normally. Exogenous addition of Fgfr2b ligands (Fgf7 and Fgf10) stimulated duct cell proliferation and inhibited endocrine cell differentiation in the ex vivo embryonic organ cultures of wild type pancreas. Our results thus suggest that Fgfr2b-mediated signaling plays a major role in pancreatic ductal proliferation and branching morphogenesis, but has little effect on endocrine and exocrine differentiation.
Pulkkinen
Mari-Anne
MA
Biomedicum Helsinki, Program for Developmental and Reproductive Biology and Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland. mari-anne.pulkkinen@helsinki.fi
Spencer-Dene
Bradley
B
Dickson
Clive
C
Otonkoski
Timo
T
D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology; D019858:Enteroendocrine Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008817:Mice, Mutant Strains; D009924:Organ Culture Techniques; D009929:Organ Size / Q000235:genetics; D010179:Pancreas / Q000002:abnormalities / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D010183:Pancreatic Ducts / Q000166:cytology / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction
D015415:Biomarkers; C496464:Fgf10 protein, mouse; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D020033:Protein Isoforms; D017468:Receptors, Fibroblast Growth Factor; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor