Tingler Melanie, Ott Tim, Tözser Janos, Kurz Sabrina, Getwan Maike, Tisler Matthias, Schweickert Axel, Blum Martin
Institute of Zoology, University of Hohenheim, Stuttgart, D-70593, Germany.
Genesis. 2014 Jun;52(6):588-99. doi: 10.1002/dvg.22766. Epub 2014 Mar 14.
Vertebrates display asymmetric arrangements of inner organs such as heart and stomach. The Nodal signaling cascade in the left lateral plate mesoderm in all cases directs asymmetric morphogenesis and placement during organogenesis. Mechanisms that lead up to left-asymmetric Nodal induction seem to differ between the vertebrates. Cilia produce a leftward extracellular fluid flow in zebrafish, medaka, mouse, rabbit, and Xenopus embryos during neurulation. In Xenopus, earlier asymmetric cues were described. Some, such as Rab11, apparently act in the zygote. Others were efficiently manipulated in ventral-right cells at the four-cell stage, a lineage presumably independent of the ciliated gastrocoel roof plate (GRP) during neurulation. Here, we show that one- and four-cell manipulations of Rab11 showed equal low efficiencies of left-right disturbances. We also reevaluated the lineage of the GRP. By tracing back future ciliated cells from the gastrula to the four-cell stage, we show that ventral cells contribute to ciliated sensory cells at the border of the GRP. Knockdown of the Nodal inhibitor Coco in the ventral right lineage resulted in embryos with ectopic right-sided Nodal and Pitx2c expression. Together, these experiments support a cilia-based mechanism of symmetry breakage in the frog Xenopus.
脊椎动物的内部器官，如心脏和胃，呈现不对称排列。在所有情况下，左侧侧板中胚层中的Nodal信号级联在器官发生过程中指导不对称形态发生和定位。脊椎动物之间导致左侧不对称Nodal诱导的机制似乎有所不同。在神经胚形成过程中，斑马鱼、青鳉、小鼠、兔子和非洲爪蟾胚胎中的纤毛会产生向左的细胞外液流。在非洲爪蟾中，更早的不对称线索也有描述。一些，如Rab11，显然在合子中起作用。其他一些则在四细胞阶段的腹侧右细胞中被有效操控，这个细胞谱系在神经胚形成过程中可能独立于有纤毛的原肠腔顶板（GRP）。在这里，我们表明对Rab11进行单细胞和四细胞操控所导致的左右干扰效率同样低。我们还重新评估了GRP的细胞谱系。通过从原肠胚追溯到四细胞阶段未来的有纤毛细胞，我们发现腹侧细胞对GRP边界处的有纤毛感觉细胞有贡献。在腹侧右细胞谱系中敲低Nodal抑制剂Coco会导致胚胎出现异位的右侧Nodal和Pitx2c表达。总之，这些实验支持了非洲爪蟾中基于纤毛的对称性打破机制。
