Transforming growth factor-beta 1 in the developing mouse pancreas: a potential regulator of exocrine differentiation

Transforming growth factor-beta 1 (TGF-beta 1) is known to regulate cell gr owth, differentiation, and function in developing mammalian systems. Alteri ng TGF-beta 1 expression in the developing pancreas has been shown to affec t both exocrine and endocrine development, suggesting that it is an importa nt regulator of pancreatic organogenesis. We proposed to examine the ontoge ny of TGF-beta 1 mRNA expression in the developing pancreas, as well as cha racterize the patterns of relative TGF-beta 1 gene expression and activity. We performed in situ hybridization for TGF-beta 1 on pancreas specimens ob tained from CD-1 mice on gestational days 12.5 (E12.5), 15.5 (E15.5), and 1 8.5 (18.5). We also isolated mRNA from the pancreas on each of these days a nd performed a semi-quantitative reverse transcriptase polymerase chain rea ction (RT-PCR) to assess relative TGF-beta 1 expression as a function of ge stational age. Finally, we performed a TGF-beta 1 ELISA with media conditio ned by embryonic pancreas from gestational days 15.5 and 18.5. By in situ h ybridization, TGF-beta 1 mRNA is expressed exclusively in the E12.5 pancrea tic epithelium, sparing the surrounding mesenchyme. As pancreatic organogen esis progresses, TGF-beta 1 mRNA expression localizes predominantly to the developing acini. TGF-PI gene expression appears modest through E15.5 but i s upregulated near the end of gestation, at E18.5. TGF-beta 1 activity, by ELISA, is also upregulated at E18.5. TGF-beta 1 may thus be a modulator of pancreatic organogenesis. Modest TGF-beta 1 expression through E15.5 may be permissive for exocrine lineage selection. TGF-beta 1 expression may then become critical for terminal acinar differentiation. Upregulated TGF-beta 1 expression at the end of gestation may be important for islet formation, a nd it may be necessary to inhibit continued proliferation and differentiati on of pluripotent cells within the pancreatic ductal epithelium.