Fig. 4.

Dissecting the role of the FGF intracellular signaling pathways in SHF explants grown for 24 hours. (A,B) Inhibiting of the Ras/Erk pathway using the MEK inhibitor had no effect on proliferation (A) but significantly increased myocardial differentiation (B) compared with controls (B,*P=0.03). Inhibition of the AKT pathway with the PI3K inhibitor decreased proliferation (A,*P=0.001) but had no effect on differentiation. Inhibition of the PKC pathway with the PLCγ inhibitor decreased proliferation (A, *P=0.001) but had no effect on differentiation. Blocking the FGF signaling with SU5402 decreased proliferation (A, *P=0.003) in the same way as the PI3K and PLC-γ inhibitors, and increased differentiation (B; *P=0.02) in the same way as the MEK inhibitor. (C,D) Treatment with low dose BMP2 (25 ng/ml) plus the MEK inhibitor did not affect proliferation. Combining BMP2 and the Mek inhibitor significantly increased myocardial differentiation compared with controls (*P=0.001) but was not significantly increased compared with BMP alone.