Abstract
Transforming growth factor-beta (TGFbeta) and adrenomedullin (AM) are multifunctional regulatory peptides that are secreted by a variety of normal and malignant cells. The TGFbetas 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 TGFbeta1 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 TGFbeta1 and AM. The early placenta, including the giant trophoblastic cells, showed high levels of staining and hybridization for TGFbeta1 and AM proteins and mRNAs. The heart was the first organ that showed expression of TGFbeta1 and AM during embryogenesis. The spatio-temporal patterns of expression of TGFbeta1 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 TGFbeta1 and AM expression. These data show colocalization of TGFbeta1 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 TGFbeta1 and AM mRNAs in all embryonic and adult mouse and rat tissues examined. Our data show that the expression of TGFbeta1 and AM is regulated in a spatial and temporal manner such that overlapping patterns of expression of TGFbeta1 and AM occur in several tissues at the same stage of development and in the same cellular location in rodent embryogenesis.
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