Characterizing a Cellular Mechanism of Cardiac Ventricular Septal Formation (2016)

Undergraduates: Caroline Tarallo, Leslie Kennedy

Faculty Advisor: Frank Conlon
Department: Biology

---

Congenital heart disease (CHD), encompassing any abnormality within the heart's anatomical structure present at birth, is the most common type of birth defect with 1.35 million babies born with lethal CHD each year. Ventricular defects account for 33% of CHD cases, occurring when the interventricular septum (IVS) does not fully develop. The septum appears to arise from the interaction between two populations of cells, one from the first heart field and another from the second heart field. However, despite severe clinical impacts of septal defects, the cellular and molecular events governing the integration and contribution of these two populations of cells to the IVS have yet to be established. To elucidate mechanisms of septation, we used a reporter mouse that allows lineage tracing of individual clones across the period of heart development. Our results show that cells within the second heart field comprise cells within the IVS. To explore the mechanisms by which these cells integrate and contribute to the IVS, we used mice that are null for the transcription factor Casz1, a gene know to be essential for mammalian IVS formation. By repeating cell fate mapping, we went on to show that there was a marked reduction in the number of secondary heart field derived clones in the IVS of Casz1 mice compared to wildtype mice. These studies have established a role for the second heart field in IVS formation and have determined the cellular requirements for Casz1 in these processes.