Alsan Burak H, Schultheiss Thomas M
Molecular Medicine Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Development. 2002 Apr;129(8):1935-43. doi: 10.1242/dev.129.8.1935.
The avian heart develops from paired primordia located in the anterior lateral mesoderm of the early embryo. Previous studies have found that the endoderm adjacent to the cardiac primordia plays an important role in heart specification. The current study provides evidence that fibroblast growth factor (Fgf) signaling contributes to the heart-inducing properties of the endoderm. Fgf8 is expressed in the endoderm adjacent to the precardiac mesoderm. Removal of endoderm results in a rapid downregulation of a subset of cardiac markers, including Nkx2.5 and Mef2c. Expression of these markers can be rescued by supplying exogenous Fgf8. In addition, application of ectopic Fgf8 results in ectopic expression of cardiac markers. Expression of cardiac markers is expanded only in regions where bone morphogenetic protein (Bmp) signaling is also present, suggesting that cardiogenesis occurs in regions exposed to both Fgf and Bmp signaling. Finally, evidence is presented that Fgf8 expression is regulated by particular levels of Bmp signaling. Application of low concentrations of Bmp2 results in ectopic expression of Fgf8, while application of higher concentrations of Bmp2 result in repression of Fgf8 expression. Together, these data indicate that Fgf signaling cooperates with Bmp signaling to regulate early cardiogenesis.
鸟类心脏由位于早期胚胎前外侧中胚层的成对原基发育而来。先前的研究发现，与心脏原基相邻的内胚层在心脏特化过程中发挥着重要作用。当前的研究提供了证据表明成纤维细胞生长因子（Fgf）信号传导有助于内胚层的心脏诱导特性。Fgf8在与心脏前中胚层相邻的内胚层中表达。去除内胚层会导致包括Nkx2.5和Mef2c在内的一部分心脏标志物迅速下调。通过提供外源性Fgf8可以挽救这些标志物的表达。此外，异位应用Fgf8会导致心脏标志物的异位表达。心脏标志物的表达仅在同时存在骨形态发生蛋白（Bmp）信号传导的区域中扩展，这表明心脏发生发生在同时暴露于Fgf和Bmp信号传导的区域。最后，有证据表明Fgf8的表达受特定水平的Bmp信号传导调节。应用低浓度的Bmp2会导致Fgf8的异位表达，而应用高浓度的Bmp2会导致Fgf8表达受到抑制。总之，这些数据表明Fgf信号传导与Bmp信号传导协同作用以调节早期心脏发生。
