Expression of the inhibitory Smad7 in early mouse development and upregulation during embryonic vasculogenesis

SMAD proteins are downstream targets of serine/threonine kinase receptors of the transforming growth factor beta (TGF beta) superfamily. Ligands activating these receptors regulate cell growth, differentiation and development in many tissues of various organisms. In mammals eight different Smad genes are known, each with different roles in mediating signalling between plasma membrane and nucleus. Smad6 and Smad7 are inhibitors of TGF beta family signalling. They are both expressed in human adult vascular endothelial cells, particularly after these cells have been subjected to shear stress (Topper et al. [1997] Proc Natl Acad Sci USA 94:9314-9319). Here we show by reverse transcriptase polymerase chain reaction and in situ hybridization that Smad7 mRNA is highly expressed in the developing vascular system of the mouse embryo but is also detectable much earlier in preimplantation embryos and during gastrulation. We also demonstrate by transient transgenesis that overexpression of Smad7 in mouse zygotes inhibits development beyond the 2-cell stage. This confirms earlier conclusions of similar, but complementary, experiments using a dominant negative type II TGF beta receptor demonstrating that TGF beta signalling is required for normal preimplantation development.