Analysis of Cripto expression during mouse cardiac myocyte differentiation.

Vertebrate cardiac progenitor cells are initially allocated in two distinct domains, the first and second heart fields. It has been demonstrated that first heart field cells give rise to the myocardial cells in the left ventricle and part of the atria, whereas second heart field cells move into the developing heart tube and contribute to the myocardium of the outflow tract and right ventricle and the majority of atria. In this study, we have examined the expression of the mouse Cripto gene and the lineage of Cripto-expressing cells, focusing on its relationship with cardiac myocyte differentiation. The mouse Cripto gene is initially expressed at late head fold (LHF) stages in the cardiac crescent region, known as the first heart field; later in the medial region of the early heart tube, and by embryonic day 8.5, it is localized to the outflow tract. Using a Cripto-LacZ allele, we found that Cripto- expressing progeny cells contribute to the myocardium of the entire outflow tract and right ventricle, as well as to a majority of cells within the left ventricle. In contrast, no Cripto- expressing progeny cells were found in the atria or atrio-ventricular canal. Therefore, Cripto is transiently expressed in early differentiating myocardial cells of the left ventricle, right ventricle and outflow tract between LHF stages and E8.5. Cripto expression is subsequently downregulated as cells undergo further differentiation.