Developmental stage-specific biphasic roles of Wnt/β-catenin signaling in cardiomyogenesis and hematopoiesis

摘要

Although Wingless (Wg)/Wnt signaling has been implicated in heart development of multiple organisms, conflicting results have been reported regarding the role of Wnt/β-catenin pathway in cardiac myogenesis: Wg/armadillo signaling promotes heart development in Drosophila, whereas activation of Wnt/β-catenin signaling inhibits heart formation in avians and amphibians. Using an in vitro system of mouse ES cell differentiation into cardiomy-ocytes, we show here that Wnt/β-catenin signaling exhibits developmental stage-specific, biphasic, and antagonistic effects on cardiomyogenesis and hematopoiesis/vasculogenesis. Activation of the Wnt/β-catenin pathway in the early phase during embryoid body (EB) formation enhances ES cell differentiation into cardio-myocytes while suppressing the differentiation into hematopoietic and vascular cell lineages. In contrast, activation of Wnt/β-catenin signaling in the late phase after EB formation inhibits cardiomyo-cyte differentiation and enhances the expression of hematopoiet-ic/vascular marker genes through suppression of bone morphoge-netic protein signaling. Thus, Wnt/β-catenin signaling exhibits biphasic and antagonistic effects on cardiomyogenesis and hematopoiesis/vasculogenesis, depending on the stage of development.