ZFIN ID: ZDB-PUB-140828-7
Blood Flow and Bmp Signaling Control Endocardial Chamber Morphogenesis
Dietrich, A.C., Lombardo, V.A., Abdelilah-Seyfried, S.
Date: 2014
Source: Developmental Cell   30: 367-377 (Journal)
Registered Authors: Abdelilah-Seyfried, Salim
Keywords: none
MeSH Terms:
  • 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*
PubMed: 25158852 Full text @ Dev. Cell
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.