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Coordinate Expression of Transforming Growth Factor-ß1 and Adrenomedullin in Rodent Embryogenesis

Department of Cell and Cancer Biology, National Cancer Institute, Medicine Branch, Rockville, Maryland 20850

Address all correspondence and requests for reprints to: Dr. Sonia B. Jakowlew, Department of Cell and Cancer Biology, National Cancer Institute, Medicine Branch, 9610 Medical Center Drive, Suite 300, Rockville, Maryland 20850. E-mail: jakowlews{at}bprb.nci.nih.gov

Transforming growth factor-ß (TGFß) and adrenomedullin (AM) are multifunctional regulatory peptides that are secreted by a variety of normal and malignant cells. The TGFßs 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 TGFß1 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 TGFß1 and AM. The early placenta, including the giant trophoblastic cells, showed high levels of staining and hybridization for TGFß1 and AM proteins and mRNAs. The heart was the first organ that showed expression of TGFß1 and AM during embryogenesis. The spatio-temporal patterns of expression of TGFß1 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 TGFß1 and AM expression. These data show colocalization of TGFß1 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 TGFß1 and AM mRNAs in all embryonic and adult mouse and rat tissues examined. Our data show that the expression of TGFß1 and AM is regulated in a spatial and temporal manner such that overlapping patterns of expression of TGFß1 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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