The Zohn laboratory is interested in understanding how genes and environment interact to cause CHDs. We utilize mouse models and alter maternal micronutrient intake to create gene-environment models to study.  For instance, we can modulate the penetrance and expressivity of CHDs in the LgDelmodel of 22q11.2 deletion syndrome by feeding pregnant mice a vitamin A-supplemented diet.  To understand the mechanisms for this interaction, we examine progenitor cell specification and early development. Our findings suggest that 22q11.2 is more susceptible to changes in maternal diet due to defective negative feedback loops that involve miRNAs required to buffer vitamin A exposures. We also study a Hectd1 model of CHDs that interacts with vitamin A deficiency to cause conotruncal defects. Finally, the Hectd1 model also exhibits a thin ventricle wall phenotype, which we demonstrate is due to defects in placental development.  We plan to utilize this new placental–heart axis model to identify the placental-derived signals that alter myocardial development.