Blood flow and Bmp signaling control endocardial chamber morphogenesis
- 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 chamberDuring 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.…
Author details: | Ann-Christin Dietrich, Veronica A. Lombardo, Salim Abdelilah-SeyfriedORCiDGND |
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DOI: | https://doi.org/10.1016/j.devcel.2014.06.020 |
ISSN: | 1534-5807 |
ISSN: | 1878-1551 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/25158852 |
Title of parent work (English): | Developmental cell |
Publisher: | Cell Press |
Place of publishing: | Cambridge |
Publication type: | Article |
Language: | English |
Year of first publication: | 2014 |
Publication year: | 2014 |
Release date: | 2017/03/27 |
Volume: | 30 |
Issue: | 4 |
Number of pages: | 11 |
First page: | 367 |
Last Page: | 377 |
Funding institution: | Deutsche Forschungsgemeinschaft (DFG); DFG [SE2016/7-1, SE2016/7-2] |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
Peer review: | Referiert |