Developmental stage-specific biphasic roles of Wnt/β-catenin signaling in cardiomyogenesis and hematopoiesis
Developmental stage-specific biphasic roles of Wnt/β-catenin signaling in cardiomyogenesis and hematopoiesis
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DOI：
10.1073/pnas.0605768103
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发表时间：
2006-12-26
影响因子：
11.1
通讯作者：
Komuro, Issei
中科院分区：
文献类型：
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作者：
Naito, Atsuhiko T.;Shiojima, Ichiro;Komuro, Issei
尽管无翅（Wg）/Wnt信号通路已被证实与多种生物的心脏发育有关，但关于Wnt/β -连环蛋白通路在心肌发生中的作用却有相互矛盾的结果报道：Wg/犰狳信号促进果蝇的心脏发育，而Wnt/β -连环蛋白信号的激活抑制鸟类和两栖类的心脏形成。利用小鼠胚胎干细胞（ES细胞）体外分化为心肌细胞的体系，我们在此表明Wnt/β -连环蛋白信号对心肌发生以及造血/血管发生呈现出发育阶段特异性、双相性和拮抗作用。在拟胚体（EB）形成的早期阶段激活Wnt/β -连环蛋白通路可促进ES细胞分化为心肌细胞，同时抑制其分化为造血和血管细胞谱系。相反，在EB形成后的晚期阶段激活Wnt/β -连环蛋白信号则抑制心肌细胞分化，并通过抑制骨形态发生蛋白信号增强造血/血管标记基因的表达。因此，Wnt/β -连环蛋白信号对心肌发生以及造血/血管发生呈现出双相性和拮抗作用，这取决于发育阶段。
Although Wingless (Wg)/Wnt signaling has been implicated in heart development of multiple organisms, conflicting results have been reported regarding the role of Wnt/beta-catenin pathway in cardiac myogenesis: Wg/armadillo signaling promotes heart development in Drosophila, whereas activation of Wnt/beta-catenin signaling inhibits heart formation in avians and amphibians. Using an in vitro system of mouse ES cell differentiation into cardiomyocytes, we show here that Wnt/beta-catenin signaling exhibits developmental stage-specific, biphasic, and antagonistic effects on cardiomyogenesis and hematopoiesis/vasculogenesis. Activation of the Wnt/beta-catenin pathway in the early phase during embryoid body (EB) formation enhances ES cell differentiation into cardiomyocytes while suppressing the differentiation into hematopoietic and vascular cell lineages. In contrast, activation of Wnt/beta-catenin signaling in the late phase after EB formation inhibits cardiomyocyte differentiation and enhances the expression of hematopoietic/vascular marker genes through suppression of bone morphogenetic protein signaling. Thus, Wnt/beta-catenin signaling exhibits biphasic and antagonistic effects on cardiomyogenesis and hematopoiesis/vasculogenesis, depending on the stage of development.