Blood Flow and Bmp Signaling Control Endocardial Chamber Morphogenesis

• Published in: Developmental cell 2014-08, Vol.30 (4), p.367-377
• Main Authors: Dietrich, Ann-Christin, Lombardo, Verónica A., Veerkamp, Justus, Priller, Florian, Abdelilah-Seyfried, Salim
• Format: Article
• Language: English
• Subjects: Animals; Bone Morphogenetic Proteins - metabolism; Cell Movement; Cell Proliferation; Endocardium - cytology; Endocardium - embryology; Endocardium - metabolism; Endothelial Cells - metabolism; Endothelial Cells - physiology; Hemodynamics; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Morphogenesis; Signal Transduction; Vascular Endothelial Growth Factor A - metabolism; Zebrafish; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2014.06.020

During heart development, the onset of heartbeat and blood flow coincides with a ballooning of the cardiac chambers. Here, we have used the zebrafish as a vertebrate model to characterize chamber ballooning morphogenesis of the endocardium, a specialized population of endothelial cells that line the interior of the heart. By combining functional manipulations, fate mapping studies, and high-resolution imaging, we show that 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 vascular endothelial growth factor (VEGF) signaling. Similar to myocardial cells, endocardial cells obtain distinct chamber-specific and inner- versus outer-curvature-specific surface area sizes. We find that the hemodynamic-sensitive transcription factor Klf2a is involved in regulating 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. [Display omitted] •Endocardial growth during ballooning stages occurs without influx of external cells•Endocardial cells acquire chamber- and region-specific surface area sizes•Bmps and blood flow regulate endocardial growth in a manner independent of VEGF•Klf2a is an important regulator of endocardial cell morphology Little is known about endocardial chamber morphogenesis. Dietrich et al. show that the endocardium is flow sensitive and has a role in adapting heart chamber growth in response to the mechanical stimulus of blood flow. Endocardial growth also requires Bmp signaling in a manner independent of VEGF-dependent angiogenesis.