Cardiac development and genetics group, Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, Utrecht, The Netherlands.
Circ Res. 2012 Feb 17;110(4):578-87. doi: 10.1161/CIRCRESAHA.111.261172. Epub 2012 Jan 12.
The importance for Bmp signaling during embryonic stem cell differentiation into myocardial cells has been recognized. The question when and where Bmp signaling in vivo regulates myocardial differentiation has remained largely unanswered.
To identify when and where Bmp signaling regulates cardiogenic differentiation.
Here we have observed that in zebrafish embryos, Bmp signaling is active in cardiac progenitor cells prior to their differentiation into cardiomyocytes. Bmp signaling is continuously required during somitogenesis within the anterior lateral plate mesoderm to induce myocardial differentiation. Surprisingly, Bmp signaling is actively repressed in differentiating myocardial cells. We identified the inhibitory Smad6a, which is expressed in the cardiac tissue, to be required to inhibit Bmp signaling and thereby promote expansion of the ventricular myocardium.
Bmp signaling exerts opposing effects on myocardial differentiation in the embryo by promoting as well as inhibiting cardiac growth.
Bmp 信号在胚胎干细胞向心肌细胞分化过程中的重要性已得到认可。但是 Bmp 信号在体内何时以及何处调节心肌分化的问题在很大程度上仍未得到解答。
确定 Bmp 信号何时何地调节心脏发生分化。
在这里，我们观察到在斑马鱼胚胎中，Bmp 信号在心脏祖细胞分化为心肌细胞之前就已经活跃。Bmp 信号在体节形成过程中在前侧板中胚层中持续需要诱导心肌分化。令人惊讶的是，Bmp 信号在分化的心肌细胞中被主动抑制。我们鉴定出抑制性 Smad6a 在心脏组织中表达，需要抑制 Bmp 信号，从而促进心室心肌的扩张。
Bmp 信号通过促进和抑制心脏生长对胚胎中的心肌分化产生相反的影响。
