It is the overall goal of this proposed research to better understand the role of Iroquois (Irx) transcription factors in the differentiation of the atrium and ventricle during cardiac development. Specifically, by misexpressing Irx4 throughout the heart in mice, we will determine whether a ventricular program of gene expression can be imposed in the atrium. Conversely, with a combination of multiple Irx-gene knockouts and the expression of a dominant negative Irx4 molecule in the ventricle, we will determine whether genetic redundancy with other Irx family members exists in the heart. Finally, we will identify enhancer elements that control ventricle-specific Irx4 expression. This combination of experimental approaches will reveal important insight into the regulation of ventricular versus atrial chamber identity, and increase the understanding of the molecular basis of congenital heart defects and abnormal heart function.
