Figure 9

Model of the intersection of retinoic acid (RA), Wnt, and BMP4 signalling during cardiac and skeletal muscle development. BMP4 upregulates Wnt/β-catenin during mesoderm induction (green arrow) and blocks skeletal myogenesis by downregulation of Meox1, Pax3 and myogenic regulatory factor expression (red inhibition arrow). This inhibition can be reversed by RA, which enhances Tob1, Wnt3a, Pax3 and Meox1 expression, activates β-catenin and inhibits BMP4 expression (green arrows). RA receptors bind directly to the Wnt3a, Meox1, and Pax3 regulatory regions (bold green arrows). RA inhibits GATA-4 expression and cardiomyogenesis, likely by inhibiting BMP4 expression and function. Grey arrows indicate previous work [references [6, 8–10, 35, 38, 40, 44, 102, 103].