UC San Diego

The atrial and ventricular chambers of the heart behave as distinct

functional subunits with unique morphological, contractile, and electrophysiological properties. Therefore, the proper differentiation of atrial and ventricular tissues is crucial for the formation of a functional heart. Although the differences between atrial and ventricular chambers are well characterized, less is known about how these chamber-specific attributes are acquired. Here, we show that the FGF signaling pathway plays an essential part in regulating ventricular chamber identity. Loss of FGF signaling following the onset of ventricular differentiation results in gradual accumulation of atrial cells, a corresponding loss of ventricular cells, and a progressive increase in the appearance of ectopic atrial cells within the ventricle. These phenotypes reflect an important role for sustained FGF signaling in maintaining chamber- specific characteristics in ventricular cardiomyocytes. In addition, FGF signaling is required to establish ventricular character in late-differentiating cardiomyocytes that append to the arterial pole of the heart. Our results highlight that, even after the initial specification of atrial and ventricular fates, ventricular identity needs to be continuously reinforced. Our studies suggest active maintenance as a pervasive developmental mechanism by which cell fates are enforced until a cell is committed. In addition, we present our findings from a phenotype-driven small molecule screen to find additional signaling pathways that modulate atrial and ventricular identities.