Fig. 8. Models of the regulation of cardiac gene expression. (A) Cardiogenesis takes place in regions where Bmp and Fgf signaling overlap. Members of the Bmp family are expressed in lateral regions of the embryo (blue). Fgf8 is expressed in the gridded areas. Within the anterior part of the embryo, cardiac gene expression occurs where Bmp and Fgf signaling overlap. Note, however, that the signals also overlap in the posterior primitive streak, although cardiogenesis does not occur in that region, indicating the presence of other regulators of cardiogenesis. (B) Molecular regulation of cardiogenesis. Nkx2.5 appears to be regulated by both Bmp and Fgf signaling, whereas Gata4 is regulated by Bmp but not by Fgf signaling. Mef2c is also regulated by both Bmp and Fgf signaling. The regulation of Mef2c by Bmp and Fgf signaling may be direct or, as Mef2c is expressed several hours after Nkx2.5 and Gata4, work indirectly through Nkx and Gata genes. See text for discussion. (C) Integration of signals that regulate cardiogenesis. Cardiac mesoderm is induced by Bmp signals from the endoderm and ectoderm (blue), and by Fgf8 signals from the endoderm (yellow). Fgf8 is itself regulated by Bmp signaling, and appears to be expressed at intermediate levels of Bmp activity. In addition, cardiac inhibitory signals are present in the embryo (red dashes), emanating from the neural plate, ectoderm or other sources. See text for discussion.
