Inhibition of Wnt activity induces heart formation from posterior mesoderm

In the chick, heart mesoderm is induced by signals from the anterior endode rm. Although BMP-2 is expressed in the anterior endoderm, BMP activity is n ecessary but not sufficient for heart formation. Previous work from our lab has suggested that one or more additional factors from anterior endoderm a re required. Crescent is a Frizzled-related protein that inhibits Wnt-8c an d is expressed in anterior endoderm during gastrulation. At the same stages , expression of Wnt-3a and Wnt-8c is restricted to the primitive streak and posterior lateral plate, and is absent from the anterior region where cres cent is expressed. Posterior lateral plate mesoderm normally forms blood, b ut coculture of this tissue with anterior endoderm or infection with RCAS-c rescent induces formation of beating heart muscle and represses formation o f blood. Dkk-1, a Wnt inhibitor of a different protein family, similarly in duces heart-specific gene expression in posterior lateral plate mesoderm. F urthermore, we have found that ectopic Wnt signals can repress heart format ion from anterior mesoderm in vitro and in vivo and that forced expression of either Wnt-3a or Wnt-8c can promote development of primitive erythrocyte s from the precardiac region. We conclude that inhibition of Wnt signaling promotes heart formation in the anterior lateral mesoderm, whereas active W nt signaling in the posterior lateral mesoderm promotes blood development. We propose a model in which two orthogonal gradients, one of Wnt activity a long the anterior-posterior axis and the other of BMP signals along the dor sal-ventral axis, intersect in the heart-forming region to induce cardiogen esis in a region of high BMP and low Wnt activity.