Activation of endogenous Smad2 modulates cardiomyogenesis in embryonic stem cells

Abstract

The role of Smads and their specific ligands during cardiomyogenesis in ES cells was examined. Smad2 was activated bimodally in the early and late phases of cardiac differentiation, while Smad1 was activated after the middle phase. Nodal and Cripto were expressed in the early stage and then down-regulated, whereas TGF-β and Activin were expressed only in the late phase. Suppression of early Smad2 activation by SB-431542 produced complete inhibition of endodermal and mesodermal induction but augmented neuroectodermal differentiation, followed by poor cardiomyogenesis, while inhibition during the late phase alone promoted cardiomyogenesis.