Recent findings emphasized a critical role for the Wnt signaling pathway during the early steps of embryogenesis, including the development of the hematopoietic system and cardiac development. To date, the role of Wnt in promoting or inhibiting development of both tissues was discussed controversialy, dependent on species and timepoint of expression. Differentiation of embryonic stem cells (ESC) recapitulates early stages of .mammalian development. In the present study, we generated murine ESC lines overexpressing Wnt-1 (Wnt1ES). When induced to differentiate towards the cardiomyocytic lineage Wnt1ES showed a significant increased ability to generate cardiomyocytes when compared with a control ESC (control ES) line. In addition, Wnt1ES cells were unable to form hematopoietic cells, whereas development of endothelial cells, a cell type closely associated with blood during embryogenesis, was comparable to control ES . Finally, cardiac differentiation was markedly decreased by the addition of the WNT antagonist Dkk-1 to the culture medium. These findings suggest that Wnt-1 may regulate differentiation of immature mesodermal cells in a tissue specific manner.