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Expression and misexpression of members of the FGF and TGFβ families of growth factors in the developing mouse pancreas
Author(s) -
Dichmann Darwin S.,
Miller Christopher P.,
Jensen Jan,
Scott Heller R.,
Serup Palle
Publication year - 2003
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.10270
Subject(s) - biology , fgf10 , pancreas , endocrinology , medicine , fibroblast growth factor , activin receptor , fibroblast growth factor receptor , pdx1 , fibroblast growth factor receptor 4 , mesenchyme , receptor , transforming growth factor , microbiology and biotechnology , embryo , insulin , genetics , islet
We have performed a high‐capacity, semiquantitative, reverse transcriptase‐polymerase chain reaction screen for expression of fibroblast growth factor (FGF) and transforming growth factor β (TGFβ) 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 TGFβ‐1 and ‐2, and constitutive expression of TGFβ‐3 and their receptors. Of the Inhibin/Activin members, we found exclusively Inhibin‐α and Activin‐βB 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. Developmental Dynamics 226:663–674, 2003. © 2003 Wiley‐Liss, Inc.