Building and Repairing the Heart: What Can We Learn from Embryonic Development?

Figure 1

Signaling events in murine heart development and cardiac ESC differentiation. In both systems, mesodermal induction from the epiblast is regulated by Wnt/𝛽-catenin, Nodal/Activin, and BMP signaling pathways and correlates with Brachyury upregulation. Further commitment of mesodermal progenitors to cardiac mesoderm and consequent first heart field (FHF) formation require the inhibition of Wnt signaling and expression of BMPs. Similarly, in ESCs system, Notch pathway inhibits Wnt/𝛽-catenin signaling and activates BMP to specify cardiac fates. Wnt/𝛽-catenin signaling is then activated to allow proliferation and maintenance of the SHF, both in embryo and ESCs. Further differentiation from the cardiac crescent stage to the following morphogenic phases of embryonic heart development and, in parallel, the expression of cardiomyocyte differentiation genes in ESCs require inhibition of Wnt/𝛽-catenin. In the embryo and ESCs, this is achieved by Notch and noncanonical Wnt signaling, which inhibit the effect of Wnt/𝛽-catenin and instruct progenitor cells within the SHF to leave the proliferative state and start differentiating. ⊣ represents inhibitory effect; ⤾ represents maintenance of a proliferative state.