Abstract
The tenacious prevalence of human pancreatic diseases such as diabetes mellitus and adenocarcinoma has prompted huge research interest in better understanding of pancreatic organogenesis. The plethora of signaling pathways involved in pancreas development is activated in a highly coordinated manner to assure unmitigated development and morphogenesis in vertebrates. Therefore, a complex mesenchymal–epithelial signaling network has been implicated to play a pivotal role in organogenesis through its interactions with other germ layers, specifically the endoderm. The Fibroblast Growth Factor Receptor FGFR2-IIIb splicing isoform (FGFR2b) and its high affinity ligand Fibroblast Growth Factor 10 (FGF10) are expressed in the epithelium and mesenchyme, respectively, and therefore are well positioned to transmit mesenchymal to epithelial signaling. FGF10 is a typical paracrine FGF and chiefly mediates biological responses by activating FGFR2b with heparin/heparan sulfate (HS) as cofactor. A substantial number of studies using genetically engineered mouse models have demonstrated an essential role of FGF10 in the development of many organs and tissues including the pancreas. During mouse embryonic development, FGF10 signaling is crucial for epithelial cell proliferation, maintenance of progenitor cell fate and branching morphogenesis in the pancreas. FGF10 is also implicated in pancreatic cancer, and that overexpression of FGFR2b is associated with metastatic invasion. A thorough understanding of FGF10 signaling machinery and its crosstalk with other pathways in development and pathological states may provide novel opportunities for pancreatic cancer targeted therapy and regenerative medicine.
Highlights
The Fibroblast Growth Factor (FGF) family of peptides and the corresponding family of receptor tyrosine kinases (RTKs) collectively constitute one of the most adaptable, complex, and diverse growth factor signaling systems that are involved in many developmental and repair processes in virtually all vertebrate and invertebrate tissues and cells (Goetz and Mohammadi, 2013)
Ectopic expression of Sonic Hedgehog (SHH) in mice driven by the Pdx1 promoter results in differentiation of the pancreatic mesenchyme into smooth muscle and the epithelium assumes an intestinal fate with the generation of few early endocrine cell types (Apelqvist et al, 1997)
Animal models lacking each of the secreted FGFs have been developed with diverse phenotypes ranging from mild abnormality in adult physiology to early embryonic lethality
Summary
The Fibroblast Growth Factor (FGF) family of peptides and the corresponding family of receptor tyrosine kinases (RTKs) collectively constitute one of the most adaptable, complex, and diverse growth factor signaling systems that are involved in many developmental and repair processes in virtually all vertebrate and invertebrate tissues and cells (Goetz and Mohammadi, 2013). Paracrine FGF-FGFR-HS signaling engages in vital roles in regulating cell proliferation, migration, survival, and differentiation during the development of the embryo (Kato and Sekine, 1999; Ornitz and Itoh, 2015).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
