Blood Flow and Bmp Signaling Control Endocardial Chamber Morphogenesis
Blood Flow and Bmp Signaling Control Endocardial Chamber Morphogenesis
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DOI：
10.1016/j.devcel.2014.06.020
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发表时间：
2014-08-25
影响因子：
11.8
通讯作者：
Abdelilah-Seyfried, Salim
中科院分区：
文献类型：
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作者：
Dietrich, Ann-Christin;Lombardo, Veronica A.;Abdelilah-Seyfried, Salim
在心脏发育期间，心跳和血液流动的开始恰好与心腔的膨胀相吻合。在这里，我们使用斑马鱼作为脊椎动物模型来描述心内膜的腔内气球形态发生，心内膜是一种排列在心脏内部的特殊的内皮细胞群。通过结合功能操作、命运图谱研究和高分辨率成像，我们证明了心内膜的生长不需要外部细胞的流入。相反，心内膜细胞的增殖受到血流和BMP信号的调节，其方式独立于血管内皮生长因子(VEGF)信号。与心肌细胞相似，心内膜细胞获得不同的腔内特定和内、外曲率特定的表面积大小。我们发现血流动力学敏感的转录因子Klf2a参与调节心内膜细胞的形态。这些发现确立了心内膜是心脏中对血流敏感的组织，在适应血流机械刺激的腔内生长方面起着关键作用。
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.