Institute of Zoology, University of Hohenheim, Garbenstrasse 30, 70593 Stuttgart, Germany.
Curr Biol. 2012 Jan 10;22(1):33-9. doi: 10.1016/j.cub.2011.11.027. Epub 2011 Dec 15.
In vertebrates, most inner organs are asymmetrically arranged with respect to the main body axis [1]. Symmetry breakage in fish, amphibian, and mammalian embryos depends on cilia-driven leftward flow of extracellular fluid during neurulation [2-5]. Flow induces the asymmetric nodal cascade that governs asymmetric organ morphogenesis and placement [1, 6, 7]. In the frog Xenopus, an alternative laterality-generating mechanism involving asymmetric localization of serotonin at the 32-cell stage has been proposed [8]. However, no functional linkage between this early localization and flow at neurula stage has emerged. Here, we report that serotonin signaling is required for specification of the superficial mesoderm (SM), which gives rise to the ciliated gastrocoel roof plate (GRP) where flow occurs [5, 9]. Flow and asymmetry were lost in embryos in which serotonin signaling was downregulated. Serotonin, which we found uniformly distributed along the main body axes in the early embryo, was required for Wnt signaling, which provides the instructive signal to specify the GRP. Importantly, serotonin was required for Wnt-induced double-axis formation as well. Our data confirm flow as primary mechanism of symmetry breakage and suggest a general role of serotonin as competence factor for Wnt signaling during axis formation in Xenopus.
在脊椎动物中，大多数内部器官相对于主体轴是不对称排列的[1]。鱼类、两栖类和哺乳类胚胎的对称性破坏取决于神经胚形成过程中细胞外液的纤毛驱动的向左流动[2-5]。这种流动诱导了不对称节段级联，从而控制不对称器官形态发生和位置[1,6,7]。在青蛙非洲爪蟾中，已经提出了一种涉及 32 细胞阶段 5-羟色胺不对称定位的替代左右生成机制[8]。然而，这种早期定位与神经胚阶段的流动之间没有出现功能联系。在这里，我们报告说，5-羟色胺信号对于指定浅中胚层（SM）是必需的，SM 产生纤毛胃腔顶板（GRP），流动发生在那里[5,9]。下调 5-羟色胺信号的胚胎中，流动和不对称性丧失。我们发现，在早期胚胎中沿主体轴均匀分布的 5-羟色胺对于提供指定 GRP 的指导信号的 Wnt 信号是必需的。重要的是，5-羟色胺对于 Wnt 诱导的双轴形成也是必需的。我们的数据证实了流动是对称性破坏的主要机制，并表明 5-羟色胺作为 Wnt 信号在非洲爪蟾轴形成过程中的能力因子的一般作用。
