Deletion of Foxm1 specifically from smooth muscle cells did not affect differentiation, but mice died immediately after birth from severe pulmonary hemorrhage, structural defects in the arterial wall and esophageal abnormalities . When Foxm1 was deleted conditionally in developing ABT-263 Bcl-2 inhibitor respiratory epithelium proliferation rates of respiratory epithelial cells were unaltered , suggesting that Foxm1 is not required for epithelial proliferation during lung development. However, deletion of Foxm1 from respiratory epithelium impaired lung maturation, decreased expression of surfactant-associated proteins SPA, SPB and SPC and delayed differentiation of type I cells from epithelial precursors causing respiratory failure after birth . Thus, Foxm1 is essential for surfactant homeostasis and lung maturation during lung development. Studies in conditional Foxm1 knockout models have shown that Foxm1 plays unique roles in different tissues during embryonic development; the cardiomyocyte-specific role of Foxm1 in heart development remains unexplored. In this study, we utilized the Cre-LoxP system to conditionally delete Foxm1 from cardiomyocytes to ascertain the cardiomyocyte- autonomous role of Foxm1 in heart development. Deletion of Foxm1 from cardiomyocytes resulted in chamber dilation and myocardial thinning, culminating in embryonic lethality in late gestation. Cardiac Foxm1 deletion caused decreased ASP1517 cardiomyocyte proliferation and altered expression of cell cycle regulators Cdc25B, Cyclin B1, nMyc, Plk-1 and p21cip1. We also identified CaMKIId, Hey2 and myocardin as new potential targets of Foxm1 signaling and mediators of myocardial thinning. This study shows that Foxm1 is critical for expression of cell cycle regulatory genes in developing cardiomyocytes and is required for proper heart development. We have previously described the generation of Foxm1 LoxP/ LoxP mice, in which LoxP sequences flank exons 4 through 7 of the Foxm1 gene encoding the DNA binding and transcriptional activation domains . Foxm1fl/fl mice were bred with Nkx2.5-Cre mice to generate Nkx2.5-Cre/Foxm1fl/fl double transgenic mice with deletion of Foxm1 from the myocardium. Using lineage tracing experiments previous studies demonstrated that Nkx2.5-Cre was expressed in the early myocardium as well as epithelium of the first pharyngeal arch .