Immunohistochemical expression of Smads 1-6 in the 15-day gestation mouse embryo: Signaling by BMPs and TGF-beta s

The eight mammalian Smad proteins mediate cellular signaling from members o f the transforming growth factor-beta (TGF-beta), bone morphogenetic protei n (BMP), and activin families. Smads 1, 5, and 8 transmit signals from BMPs , while Smads 2 and 3 transmit signals from TGF-betas and activin, Smad 4 i s a common mediator of both pathways, while Smads 6 and 7 inhibit signaling . Signal transduction involves translocation of Smad complexes to the nucle us and subsequent gene activation. Little is known about the expression of endogenous Smad proteins during development. We identified commercially ava ilable Smad antibodies that specifically recognize a unique Smad protein an d are suitable for immunohistochemistry. Here we compare the localization o f Smads 1, 2, 3, 4, 5, and 6 in tissues of the 15-day gestation mouse embry o. Immunoreactive Smad proteins are seen in many tissues with differences i n the localization being dependent upon the cell type. All tissues express Smad 4 and at least one each of the BMP-specific and TGF-beta -specific Sma ds, while expression of Smad 6 is more restricted. Differences are observed in the nuclear versus cytoplasmic localization among the Smads in differen t cell types or tissues, suggesting selective activation of Smads during th is stage of development. Published 2001 Wiley-Liss, Inc.(dagger).