Endocardial chamber differentiation: Cell morphology.

ANN-CHRISTIN DIETRICH; VERÓNICA A. LOMBARDO; SALIM ABDELILAH-SEYFRIED

Madrid

Congreso; Weinstein Cardiovascular Conference; 2014

During heart development, the onset of heartbeat and blood flow coincides with an enlargement and incongruent ballooning of the cardiac chambers, which is essential for cardiac function. While myocardial chamber ballooning has been well characterized, little is known about endocardial chamber morphogenesis and its genetic control. Here we have used the zebrafish as a vertebrate model to characterize endocardial chamber morphogenesis and study the impact of blood flow on this process. We have combined functional manipulations and high-resolution imaging in zebrafish to show that endocardial cells obtain distinct chamber- and region-specific surface areas and shapes. We found that perturbations of hemodynamic forces produce abnormally ballooning hearts. In particular, shear stress is the major hemodynamic force responsible for cell surface enlargement within both chambers. Moreover, our results reveal that onset of flow leads to expression of the mechanosensitive transcription factor Klf2a, which restricts endocardial cell sizes. Our finding suggests that the endocardium is a specialized region within the endothelial network that is able to sense and respond to hemodynamic forces during heart development. This has a strong effect on both endocardial and myocardial morphogenesis.