Morphogens act through only a few signalling pathways but elicit many different cellular responses during development. In their investigation of how morphogens accomplish this, Brugger and colleagues identify a bone morphogenetic protein (BMP)-responsive element in the mouse Msx2gene, a target of BMP signalling (see p. 5153). Consensus Smad-binding sites and a consensus homeodomain sequence within the 52-bp core of this element are both needed for general BMP responsiveness in mouse cells and embryos; ancillary elements mediate signalling in diverse developmental settings. The sequence of the minimal BMP-responsive element, although conserved in mammals, is absent from other vertebrates and non-vertebrates. Even so, provided both Smad and homeodomain sites are present, the core Msx2 BMP-responsive element responds to Dpp signals when introduced into Drosophila embryos. Thus, synergistic interactions between homeodomain and Smad-related proteins may be an ancient mechanism for mediating the transcriptional activation of BMP/Dpp-regulated genes.