The gene Nkx2.5 has been recognized to be important in heart development, although all of its functions have not been clarified. Separately, what are known as Wnt signals are also recognized to be important in heart development. In this study, it was found that one function of Nkx2.5 is to directly control expression of the Wnt agonist Rspo3 and thereby support Wnt signaling. This in turn controls the choice of progenitor cell behavior between proliferation and differentiation that results in proper heart morphogenesis. A number of congenital heart defects were observed when Nkx2.5, Rspo3, or related genes and processes were experimentally interrupted.