Blood flow and Bmp signaling control endocardial chamber morphogenesis

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

Berlin

Congreso; 10th International BMP Conference; 2014

During vertebrate embryonic development, the primitive heart tube is comprised of cardiomyocytes and of endocardium, a specialized population of endothelial cells that line the interior of the primitive heart tube. The onset of a heartbeat and blood flow coincides with an enlargement, S-shaping and an incongruent ballooning of the atrial and ventricular cardiac chambers. We use zebrafish as a vertebrate model to analyze the molecular mechanism(s) underlying the process of endocardial cell growth during chamber development. We have combined functional manipulations, fate mapping studies, and high-resolution imaging in zebrafish to show that in striking contrast to the growth of the myocardium, which is mainly due to the addition of cells derived from the secondary heart field, endocardial growth occurs without an influx of external cells. Instead, endocardial cell proliferation is regulated, both by blood flow and by Bmp signaling in a manner independent of Vegf signaling. During ballooning stages, endocardial cells obtain distinct chamber- and inner-versus-outer-curvature-specific surface area sizes. We also find that the hemodynamic-sensitive transcription factor Klf2a is an important regulator of endocardial cell morphology. These findings establish the endocardium as the flow-sensitive tissue in the heart with a key role in adapting chamber growth in response to the mechanical stimulus of blood flow.