At E8.5-9.0, majority of cells in the mouse embryo are in active proliferation while cardiomyocytes in the heart tube are proliferatively quiescent.To understand the regulation of cardiomyocyte proliferation in the heart tube, we deleted Pten, a negative regulator of cell proliferation in the cardiac progenitors through Mesp1-Cre mediated excision.We found that deletion of Pten had little impact on cardiomyocyte proliferation in the heart tube at E8.5.Instead, we observed profoundly increased cell proliferation of the second heart field (SHF) progenitors resulting in enlarged size of the right ventricle and the outflow tract (OFT).Furthermore, we found that BMP signaling was supperssed while beta-catenin activity was enhanced in the SHF progenitors upon inactivation of Pten.As removal of Akt1 nearly completely rescued the phenotype of Pten deletion, we concluded that Akt1 signaling coordinate BMP signaling and beta-catenin activity to regulate the SHF progenitor proliferation.Nkx2-5 is an essential transcription factor for heart development and is involved in the SHF development.We uncovered a novel regulatory mechanism of Nkx2-5 mRNA post-transcription that controls its stability and translation.Finally, I will present data on cardiomyocyte regeneration in the neonatal mice.