title: Blood flow and Bmp signaling control endocardial chamber morphogenesis.
abstract: 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.
authors.affiliation: Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Straße 24-25, 14476 Potsdam, Germany; Institute for Molecular Biology, Medizinische Hochschule Hannover, Carl-Neuberg Straße 1, 30625 Hannover, Germany; Max Delbrück Center for Molecular Medicine, Robert-Rössle Straße 10, 13125 Berlin, Germany.
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Dietrich
authors.affiliation: Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Straße 24-25, 14476 Potsdam, Germany; Institute for Molecular Biology, Medizinische Hochschule Hannover, Carl-Neuberg Straße 1, 30625 Hannover, Germany; Max Delbrück Center for Molecular Medicine, Robert-Rössle Straße 10, 13125 Berlin, Germany.
authors.forename: Verónica A
authors.initials: VA
authors.lastname: Lombardo
authors.forename: Justus
authors.initials: J
authors.lastname: Veerkamp
authors.forename: Florian
authors.initials: F
authors.lastname: Priller
authors.affiliation: Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Straße 24-25, 14476 Potsdam, Germany; Institute for Molecular Biology, Medizinische Hochschule Hannover, Carl-Neuberg Straße 1, 30625 Hannover, Germany; Max Delbrück Center for Molecular Medicine, Robert-Rössle Straße 10, 13125 Berlin, Germany. Electronic address: salim.seyfried@uni-potsdam.de.
authors.forename: Salim
authors.initials: S
authors.lastname: Abdelilah-Seyfried
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D004699:Endocardium / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology; D006439:Hemodynamics; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; C436494:Klf2a protein, zebrafish; D051741:Kruppel-Like Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D029961:Zebrafish Proteins