Life is full of decisions. One of the earliest is that facing embryonic mesoderm, which must decide whether to become heart or blood. Three papers from the Lassar and Mercola groups published in a recent issue of Genes & Development show that this decision is influenced by opposing gradients of positive and negative signals that intersect to create a specific heart-forming zone in the embryo (1-3). The idea that overlapping gradients of signaling molecules can generate sharp boundaries of gene expression in the embryo is not new. What makes these papers interesting, however, is that they shed light on the signaling molecules responsible for the formation of heart and blood, the first specialized mesodermal tissues to develop in vertebrate embryos. They also suggest potential strategies for the eventual therapeutic manipulation of cardiac and blood cell fates.

The heart forms soon after gastrulation in a specific region of the anterior mesoderm adjacent to the endoderm; blood cells arise from the posterior mesoderm (4). Experiments with surgically manipulated embryos suggest that antagonistic signals control the decision of early mesodermal cells to become heart or blood (5-7). The heart does not form if anterior endoderm is extirpated from embryos, pointing to an instructive role for anterior endoderm in this process. Furthermore, when combined with posterior mesoderm in vitro, anterior but not posterior endoderm induces heart formation at the expense of blood development (5, 6).