Wnt antagonism initiates cardiogenesis in Xenopus laevis
Wnt antagonism initiates cardiogenesis in Xenopus laevis
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DOI：
10.1101/gad.855601
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发表时间：
2001-02-01
影响因子：
10.5
通讯作者：
Mercola, M
中科院分区：
文献类型：
--
作者：
Schneider, VA;Mercola, M
非洲爪哇的心脏诱导发生在背前中胚层的配对区域，以响应Spemann组织者和潜在的背前内胚层的信号。这些组织加在一起足以在非心源性腹缘中胚层诱导心脏形成。类似地，在鸟类中，潜在的最终内胚层诱导心脏前中胚层的心脏发生。两栖动物中的心脏诱导因子尚不清楚，尽管某些BMPs和EGF可以模拟鸟类心脏发生的各个方面，但两者都不能诱导诱导组织引发的全部活动。在此，我们报道了Wnt拮抗剂DKK-1和新月体可以诱导腹侧边缘带中胚层外植体形成心脏。其他Wnt拮抗剂，包括卷曲的含有结构域的蛋白Frzb和Sz1，缺乏这种活性。与Wnt拮抗不同的是，抑制BMP信号不会促进心脏的生成。异位表达GSK3β抑制了β-连环素介导的Wnt信号转导，也诱导了腹侧中胚层的心脏发生。对原肠形成过程中表达的Wnt蛋白的分析表明，Wnt3a和Wnt8而不是Wnt5A或Wnt11抑制了内源心脏的诱导。这些结果表明，组织者中DKK-1和新月的扩散通过建立WNT3a和WNT8的低活性区域启动了相邻中胚层的心脏发生。
Heart induction in Xenopus occurs in paired regions of the dorsoanterior mesoderm in response to signals from the Spemann organizer and underlying dorsoanterior endoderm. These tissues together are sufficient to induce heart formation in noncardiogenic ventral marginal zone mesoderm. Similarly, in avians the underlying definitive endoderm induces cardiogenesis in precardiac mesoderm. Heart-inducing factors in amphibians are not known, and although certain BMPs and EGFs can mimic aspects of cardiogenesis in avians, neither can induce the full range of activities elicited by the inducing tissues. Here we report that the Wnt antagonists Dkk-1 and Crescent can induce heart formation in explants of ventral marginal zone mesoderm. Other Wnt antagonists, including the frizzled domain-containing proteins Frzb and Sz1, lacked this activity. Unlike Wnt antagonism, inhibition of BMP signaling did not promote cardiogenesis. Ectopic expression of GSK3 beta, which inhibits beta -catenin-mediated Wnt signaling, also induced cardiogenesis in ventral mesoderm. Analysis of Wnt proteins expressed during gastrulation revealed that Wnt3A and Wnt8, but not Wnt5A or Wnt11, inhibited endogenous heart induction. These results indicate that diffusion of Dkk-1 and Crescent from the organizer initiate cardiogenesis in adjacent mesoderm by establishing a zone of low Wnt3A and Wnt8 activity.