The ontogeny of TGF-beta 1, -beta 2, -beta 3, and TGF-beta receptor-II expression in the pancreas: Implications for regulation of growth and differentiation

Background/Purpose: The transforming growth factor-p (TGF-beta) cytokines a re important regulators of growth and differentiation in multiple mammalian organ systems. Recent studies suggest that they may play a significant rol e in the regulation of pancreatic organogenesis. The authors proposed to ex amine the ontogeny of expression of the TGF-P cytokine isoforms (TGF-beta 1 , beta 2, and beta 3), as well as that of the type II TGF-beta receptor (T beta RII), in the pancreas. We hypothesized that their patterns of expressi on might help to clarify the manner in which they influence the development of this organ. Methods: Embryos from pregnant CD-1 mice were harvested on gestational days 12.5, 15.5, and 18.5. Microdissection was performed on the embryos to isol ate their pancreases. The pancreases were fixed, frozen embedded, and secti oned with a cryostat. Immunohistochemistry was performed using polyclonal a ntibodies to TGF-beta 1, beta 2, and beta 3, and T beta RII. Results: The patterns of expression of TGF-beta 1, beta 2, and beta 3 were similar throughout gestation. They were all present, though weakly, early i n the development of the pancreas, in the E12.5 epithelial cells. Their exp ression persisted and became localized to the acinar cells later in gestati on. T beta RII staining was present in both the E12.5 epithelial cells and the surrounding mesenchyme. As the pancreas developed, T beta RII became st rongly expressed in the ductal epithelial cells with only minimal staining in the acinar and endocrine cells. Conclusions TGF-beta s may play a role in regulating pancreatic organogenes is. Our data suggest that they may be required for the normal development o f acini. As in other cell systems, TGF-beta 1 may act as a suppressor of pa ncreatic cellular growth and differentiation. The localization of T beta RI I to the mature ductal epithelium may indicate a need for ongoing regulatio n of growth and differentiation in the pancreatic ducts beyond the fetal pe riod. Copyright (C) 1999 by W.B. Saunders Company.