The heart cells are specified in anterior mesoderm by proteins such as Dickkopf-1, Nodal, and Cerberus secreted by the anterior endoderm. Whether Dickkopf-1 and Nodal act directly on the cardiac mesoderm is the subject of research, but it seems that at least they act indirectly by stimulating the production of additional factors from the anterior endoderm. These early signals are essential for heart formation such that removal of the anterior endoderm blocks heart formation. Anterior endoderm is also sufficient to stimulate heart differientation since it can induce non-cardiogenic mesoderm from more posterior positions in the embryo to form heart.