Ontogeny of fibroblast growth factors in the early development of the rat endocrine pancreas.

Pancreatic islet ontogeny involves endocrine cell neogenesis from ductal epithelium and islet expansion by cell replication, balanced by apoptotic deletion of endocrine cells which, in rat, is pronounced in the neonate. Fibroblast growth factors (FGF) are involved in tissue morphogenesis, and we examined the distribution and ontogeny of several FGF within rat pancreas from late fetal life until weaning. Islet cell replication (immunohistochemistry for proliferating cell nuclear antigen) did not change, but a transient increase in ductal epithelial cell replication existed between postnatal days (pnd) 10 and 14. Immunoreactive FGF-1 was found mainly in alpha cells of islets, and FGF-2 immunoreactivity and mRNA throughout the islets, their distribution increasing with age. Both FGF-1 and -2 were also located in ductal epithelium, being maximally distributed at pnd 10-14, coincident with increased cell replication, and when mRNA transcripts encoding FGF-1 (4.4 kb) and FGF-2 (7 kb) were relatively increased in pancreata. FGF-4 and -6 immunoreactivities were localized strongly within islets and ductal cells. In contrast, immunoreactive FGF-7 was associated with pancreatic mesenchyme and intra-and extraislet endothelial cells, and mRNA abundance was transiently increased between pnd 4 and 12, suggesting a role in the initiation of endocrine cell neogenesis. Exogenous FGF-7 was fivefold more potent than FGF-1 or -2 in stimulating DNA synthesis within isolated rat islets. Multiple FGF are expressed within defined compartments of developing pancreas and may contribute to endocrine cell neogenesis and islet function.