Congenital heart valve defects are the leading cause of infant morbidity and mortality. Understanding how valves form during development might provide insight into the processes that go awry in congenital valve disease.
A critical step in early valve formation is the choice an endocardial cell makes between two fates: change types (endocardial to mesenchymal transformation, EMT) and contribute to the valve core, or remain an endocardial cell that can divide and generate the elongated valve leaflet. H. Scott Baldwin and colleagues now report in the July 8 Circulation Research that a transcription factor called Nfatc1, which modulates gene expression, regulates the cell-fate decisions of endocardial cells. The researchers found that Nfatc1 inhibits EMT in the developing valve (by suppressing two factors that initiate EMT). They conclude that Nfatc1 expression levels determine the allocation of endocardial cells to their two fates.
The findings suggest that mutations in the Nfatc1 gene may contribute to human congenital heart valve disease.
This research was supported by the American Heart Association, the National Heart, Lung, and Blood Institute, and the March of Dimes.