Acquisition of a cardiac fate by embryonic mesodermal cells is a fundamental step in heart formation. Heart development in frogs and avians requires positive signals from adjacent endoderm, including bone morphogenic proteins, and is antagonized by a second secreted signal, Wnt proteins, from neural tube. By contrast, mechanisms of mesodermal commitment to create heart muscle in mammals are largely unknown. In addition, Wnt-dependent signals can involve either a canonical @entity3546 pathway or other, alternative mediators. Here, we tested the involvement of Wnts and @entity3546 in @entity1 cardiac myogenesis by using a pluripotent @entity19 cell line (P19CL6) that recapitulates early steps for cardiac specification. In this system, early and late cardiac genes are up-regulated by 1% @entity3733 , and spontaneous beating occurs. Notably, @entity13020 and @entity13024 were induced days before even the earliest cardiogenic transcription factors. @entity3733 induced biochemical mediators of Wnt signaling (decreased phosphorylation and increased levels of @entity3546 ), which were suppressed by Frizzled-8Fc, a soluble Wnt antagonist. @entity3733 provoked T cell factor-dependent transcriptional activity; thus, induction of Wnt proteins by @entity3733 was functionally coupled. Frizzled-8Fc inhibited the induction of cardiogenic transcription factors, cardiogenic growth factors, and sarcomeric myosin heavy chains. Likewise, differentiation was blocked by constitutively active glycogen synthase kinase 3beta, an intracellular inhibitor of the Wntbeta-catenin pathway. Conversely, @entity13557 , which inhibits glycogen synthase kinase 3beta, and @entity13020 -conditioned medium up-regulated early cardiac markers and the proportion of differentiated cells. Thus, Wntbeta-catenin signaling is activated at the inception of @entity1 cardiac myogenesis and is indispensable for cardiac differentiation, at least in this pluripotent model system.

A Wnt- and XXXX -dependent pathway for @entity1 cardiac myogenesis.

@entity1 :: ('9606', 'Species') :: ['mammalian'] @entity13557 :: ('MESH:D018021', 'Chemical') :: ['lithium chloride'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity3733 :: ('MESH:D004121', 'Chemical') :: ['DMSO'] @entity3546 :: ('1499', 'Gene') :: ['beta-catenin'] @entity13020 :: ('89780', 'Gene') :: ['Wnt3A'] @entity13024 :: ('7478', 'Gene') :: ['Wnt8A']
@entity3546 :: (1499,Gene) :: ['beta -catenin']
