Heart PP

When an embryo is 2 weeks old, the heart muscles know their fate and they rearrange themselves in a crescent shape. Cells go to specific places and act as progenitors to form different parts like the atria, ventricles. By the third week, a tube forms that starts beating that later becomes the right ventricle. Other cells become the left ventricle. As time goes by the cells become more specific in terms of location. Newborns usually present problem only in a localized area, example, they could be born with all the chambers completely intact, but missing the right ventricle. They must have had a mutation in the cells responsible for the right ventricle that caused such a phenotype. Animal models such as chick, mouse, zebrafish embryos etc have been used to understand this process on a molecular level. However, animal models were difficult to study for very early stages. Thus, induced pluripotent stem cells became handy in order to study such preliminary phases. These cells mimic the cardiomyocytes in vivo. Together with stem cells in a dish and animal models, it was possible to understand the gene networks that chalk out the map for cardiac fate. His team was able to figure out the key components in the gene network: the Notch1, Gata4, Tbx5, Nkx2.5 and Ptnp11 are genes that are responsible for the creation of the chambers. Heterozygous mutations (mutation of a single allele) in these genes can cause the defect. It is not necessary for the mutation to be a loss of function mutation; even when the dosage of the gene was reduced, they observed the same phenotype. So this suggested that by raising the dosage of the genes, it would be possible to reverse the defect.