The Flk1 gene, which encodes a VEGF-A receptor, is expressed in the multipotent mesodermal progenitor cells of mouse embryos that give rise to various haemato-cardiovascular cell lineages. FLK1 expression also marks haemato-cardiovascular cell lineages in differentiating human embryonic stem (ES) cells, lineages that could be useful for the treatment of human cardiovascular diseases if the molecular regulation of Flk1 expression can be unravelled. Masatsugu Ema and colleagues now identify a novel enhancer in the mouse Flk1 gene that is required for the mesodermal expression of Flk1 in the early embryo and in differentiating ES cells (see p. 5357). This enhancer region, they report, is activated by Bmp, Wnt and Fgf, and contains binding sites for the transcription factors Gata, Cdx, Tcf/Lef, ER71/Etv2 and Fox, all of which are controlled by Bmp, Wnt and Fgf signalling. The researchers suggest, therefore, that early Flk1 expression might be induced by cooperative interactions between this set of transcription factors under the control of Bmp, Wnt and Fgf signalling.