Expression and misexpression of members of the FGF and TGFbeta families of growth factors in the developing mouse pancreas.
We have performed a high-capacity, semiquantitative, reverse transcriptase-polymerase chain reaction screen for expression of fibroblast growth factor (FGF) and transforming growth factor beta (TGFbeta) family genes as well as their cognate receptors. By using cDNA prepared from embryonic day 12 to postnatal day 0 embryonic mouse pancreas, we have identified several factors potentially involved in the development of the endocrine pancreas. We find high-level early expression of TGFbeta-1 and -2, and constitutive expression of TGFbeta-3 and their receptors. Of the Inhibin/Activin members, we found exclusively Inhibin-alpha and Activin-betaB to be expressed, and the BMP family was represented by BMP4, BMP5, and BMP7. The predominant forms of the BMP and Activin type II receptors were ActR-IIB and BMPR-II and of the type I receptors, BMPR-1A and -1B were the highest expressed. FGF1, FGF7, FGF9, FGF10, FGF11, and FGF18 were also expressed in the pancreas at varying time points and levels, as well as FGF receptor forms FGFR1b, FGFR1c, FGFR2b, FGFR2c, FGFR3b, and FGFR4. To gain insight into the biological function, we misexpressed members of these families in the pancreas by using the early pancreas promoter Pdx1. Misexpression of FGF4 results in disruption of the pancreas morphology with epithelial structures interspersed in stroma tissue. The endocrine compartment was reduced to scattered single cells, and the exocrine consisted of unbranched ductal epithelia with acinar structures budding off. In contrast, misexpression of BMP-6 resulted in complete agenesis of the pancreas and reduced the size of the stomach and spleen dramatically and caused fusion of the liver and duodenum.
Dichmann
Darwin S
DS
Department of Developmental Biology, Hagedorn Research Institute, Gentofte, Denmark.
Miller
Christopher P
CP
Jensen
Jan
J
Scott Heller
R
R
Serup
Palle
P
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000235:genetics*; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D028322:Inhibin-beta Subunits / Q000235:genetics; D007265:Inhibins / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010179:Pancreas / Q000196:embryology* / Q000502:physiology*; D011247:Pregnancy; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3
D019485:Bone Morphogenetic Proteins; C496464:Fgf10 protein, mouse; C496454:Fgf7 protein, mouse; C496460:Fgf9 protein, mouse; D051526:Fibroblast Growth Factor 10; D051525:Fibroblast Growth Factor 9; C508961:Tgfb1 protein, mouse; C509045:Tgfb3 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; C113569:fibroblast growth factor 18; C094377:inhibin-alpha subunit; D016220:Fibroblast Growth Factor 1; D051523:Fibroblast Growth Factor 7; D007265:Inhibins; D005346:Fibroblast Growth Factors; D028322:Inhibin-beta Subunits