A role for bone morphogenetic protein signaling in cardiomyocyte differentiation.

Elucidating molecular mechanisms that regulate induction of cardiomyocyte differentiation is important because it may lead to practical therapeutic application for tissue regeneration in various heart diseases. Recent studies have demonstrated that some growth factors regulate expression of cardiac transcription factors and play a pivotal role in cardiac development. This study investigated the roles of bone morphogenetic proteins (BMPs) and their downstream molecules, using P19CL6 cardiomyogenic cell lines. Several lines of evidence show that BMPs are indispensable for cardiomyocyte differentiation and induce differentiation through two cardiac transcription factors, Csx/Nkx2-5 and GATA-4. Furthermore, it was demonstrated that not only Smads and TAK1, important mediators of transforming growth factor-beta signaling, but also their common target, ATF-2 transcription factor, play a critical role in cardiomyocyte differentiation.