COORDINATE EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-1 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 developin g organs and adults, and their tissue distribution pattern has possibl e significance for signaling roles in many epithelial-mesenchymal inte ractions. AM is also expressed in a variety of embryonic and adult tis sues. The present study reports a comparison of the patterns of expres sion of the proteins and messenger RNAs (mRNAs) for TGF beta 1 and AM in the developing mouse embryo. Immunohistochemical and in situ hybrid ization analyses were performed on formalin-fixed paraffin-embedded se ctions of developing embryonic mouse tissues using specific antibodies and complementary RNA probes for TGF beta 1 and AM. The early placent a, including the giant trophoblastic cells, showed high levels of stai ning and hybridization for TGF beta 1 and AM proteins and mRNAs. The h eart was the first organ that showed expression of TGF beta 1 and AM d uring 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 simi larities. The lung, kidney, and intestine, in which epithelial-mesench ymal interactions occur, showed similar patterns of TGF beta 1 and AM expression. These data show colocalization of TGF beta 1 and AM in spe cific cell types associated with several tissues in the developing mou se embryo. Additionally, RT-PCR amplification and Northern blot hybrid ization showed expression of TGF beta 1 and AM mRNAs in all embryonic and adult mouse and rat tissues examined. Our data show that the expre ssion of TGF beta 1 and AM is regulated in a spatial and temporal mann er such that overlapping patterns of expression of TGF beta 1 and AM o ccur in several tissues at the same stage of development and in the sa me cellular location in rodent embryogenesis.