FIBROBLAST-GROWTH-FACTOR-2 PROMOTES PANCREATIC EPITHELIAL-CELL PROLIFERATION VIA FUNCTIONAL FIBROBLAST-GROWTH-FACTOR RECEPTORS DURING EMBRYONIC LIFE

Several investigators have postulated that soluble growth factors are involved in the early development of the pancreas. In many tissues in which soluble factors are implicated in development, these factors act on their target cells through tyrosine kinase receptors. Because we h ad some preliminary evidence that fibroblast growth factor receptors ( FGFRs) mere expressed in the early pancreas, me investigated the effec t of fibroblast growth factors (FGFs) during embryonic pancreatic deve lopment. For that purpose, we first studied the distribution and the f unctionality of FGFRs during pancreatic organogenesis. FGFR1 and FGFR4 were shown to be expressed at a high level during early pancreatic de velopment before embryonic day 16, their levels of expression decreasi ng thereafter. The functionality of FGFR was studied next. It was demo nstrated in vitro that both FGF1 and FGF2 induce the expression of NGF I-A mRNA, a useful indicator of functional growth factor-signaling pat hways. Finally, the effect of FGF2 on embryonic pancreatic epithelial cell proliferation was studied. It was shown that FGF2 induces the pro liferation of pancreatic epithelial cells during embryonic life. Taken together these data strongly suggest that FGFs are implicated in panc reatic development during embryonic life.