The small molecule BMP inhibitor, dorsomorphin, induces cardiomyogenesis in mouse ES cells.
(A) Chemical structures of dorsomorphin (DM), a selective BMP inhibitor, and 676489, a DM analog which inhibits VEGF/VEGFR2, but not BMP signaling. (B) ES cells treated with dorsomorphin (DM) from day −3 to 2 formed large areas of contracting cardiomyocytes that expressed DsRed-Nuc under the α-MHC promoter by day 12 of differentiation (right), but DMSO-treated cells did not (left). Upper panels depict representative red fluorescence images. Lower panels show the corresponding bright-field images. (C, D) Dorsomorphin treatment resulted in strong increases in expression of cardiac markers Nkx2.5 (*p = 0.021, **p = 0.020, #p = 0.0013), and Myh6 (*p = 0.046, **p = 0.026). Q-PCR results represent relative expression normalized to that of DMSO-treated cells at Day 0. Measurements were from at least three independent experiments for each time-point.