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

Abstract

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.

Hnf1b controls pancreas morphogenesis and the generation of Ngn3+ endocrine progenitors

“…Activation of the fibroblast growth factor (FGF) pathway via binding of mesenchymal FGFs to epithelial FGF receptors (FGFRs) is fundamental to promote proliferation of early pancreatic MPCs, especially through the Fgf10/Fgfr2b pathway (Bhushan et al, 2001;Hart et al, 2003;Pulkkinen et al, 2003). Surprisingly, we observed no difference in Fgfr2b expression in Pdx1-Cre;Hnf1b…”

Rbp‐j regulates expansion of pancreatic epithelial cells and their differentiation into exocrine cells during mouse development

“…During prostate develop- ment, Notch1-expressing cells defined the progenitor cells in the prostatic epithelial cell lineage, and ablation of Notch signaling in those cells inhibits the branching morphogenesis, growth, and differentiation (Wang et al, 2004). In the pancreas, disturbed branching morphogenesis also occurs in mice deficient in Fgf10 or its high-affinity receptor Fgfr2-IIIb (Bhushan et al, 2001;Pulkkinen et al, 2003). Furthermore, the overexpression of Fgf10 in the pancreatic epithelium causes increased proliferation and the persistent upregulation of Notch components in the epithelium (Norgaard et al, 2003;Hart et al, 2003).…”

Characterization of Endocrine Progenitor Cells and Critical Factors for Their Differentiation in Human Adult Pancreatic Cell Culture

“…Hybridization signals were visualized using a Bio-imaging analyzer (Fuji Photo Film). The hybridization signals were normalized by the housekeeping gene cyclophilin (28). Transplantation of CHIBs.…”