Coordinate expression of transforming growth factor-β1 and adrenomedullin in rodent embryogenesis

Transforming growth factor-beta (TGF beta) and adrenomedullin (AM) are multifunctional regulatory peptides that are secreted by a variety of normal and malignant cells. The TGF beta s are expressed in developing organs and adults, and their tissue distribution pattern has possible significance for signaling roles in many epithelial-mesenchymal interactions. AM is also expressed in a variety of embryonic and adult tissues. The present study reports a comparison of the patterns of expression of the proteins and messenger RNAs (mRNAs) for TGF beta 1 and AM in the developing mouse embryo. Immunohistochemical and in situ hybridization analyses were performed on formalin-fixed paraffin-embedded sections of developing embryonic mouse tissues using specific antibodies and complementary RNA probes for TGF beta 1 and AM. The early placenta, including the giant trophoblastic cells, showed high levels of staining and hybridization for TGF beta 1 and AM proteins and mRNAs. The heart was the first organ that showed expression of TGF beta 1 and AM during embryogenesis. The spatio-temporal patterns of expression of TGF beta 1 and AM in cardiovascular, neural, and skeletal-forming tissues as well as in the main embryonic internal organs showed striking similarities. The lung, kidney, and intestine, in which epithelial-mesenchymal interactions occur, showed similar patterns of TGF beta 1 and AM expression. These data show colocalization of TGF beta 1 and AM in specific cell types associated with several tissues in the developing mouse embryo. Additionally, RT-PCR amplification and Northern blot hybridization showed expression of TGF beta 1 and AM mRNAs in all embryonic and adult mouse and rat tissues examined. Our data show that the expression of TGF beta 1 and AM is regulated in a spatial and temporal manner such that overlapping patterns of expression of TGF beta 1 and AM occur in several tissues at the same stage of development and in the same cellular location in rodent embryogenesis.