Cilia-driven leftward flow determines laterality in Xenopus
Cilia-driven leftward flow determines laterality in Xenopus
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DOI：
10.1016/j.cub.2006.10.067
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发表时间：
2007-01-09
期刊：
影响因子：
9.2
通讯作者：
Blum, Martin
中科院分区：
文献类型：
--
作者：
Schweickert, Axel;Weber, Thomas;Blum, Martin
在胚胎发育期间确定脊椎动物的左右身体轴会导致大多数内部器官的不对称发育和放置[1，2]。尽管非对称节级联在所有脊椎动物中都是保守的，但对称性破坏的机制仍然存在争议[3]。在哺乳动物和鱼类胚胎中，需要纤毛驱动的细胞外液向左流动才能启动节级联。这种血流分别位于后脊索(“结节”)和库普弗氏囊泡[4-7]。然而，在青蛙和鸡的胚胎中，从卵裂阶段到原肠形成，分子不对称是更早需要的[8，9]。因此，纤毛机制对所有脊椎动物的有效性受到了质疑[3]。在这里，我们表明，在非洲爪蛙中，纤毛驱动的向左流动先于不对称的结节表达。在神经化过程中，胃腔顶板上出现了可活动的单纤毛，并从最初的中心位置向细胞的后极延长和极化。同时，从第15阶段开始，在LET侧板中胚层在第19阶段开始不对称节状转录之前，就出现了强劲的向左流体流动。向原肠注入1.5%的甲基纤维素阻止了向左流动，并导致了偏侧缺陷，表明流动本身是不对称基因表达和器官放置所必需的。
Determination of the vertebrate left-right body axis during embryogenesis results in asymmetric development and placement of most inner organs [1, 2]. Although the asymmetric Nodal cascade is conserved in all vertebrates, the mechanism of symmetry breakage has remained controversial [3]. In mammalian and fish embryos, a cilia-driven leftward flow of extracellular fluid is required for initiation of the Nodal cascade. This flow is localized at the posterior notochord ("node") and Kupffer's vesicle, respectively [4-7]. In frog and chick embryos, however, molecular asymmetries are required earlier, from cleavage stages through gastrulation [8, 9]. The validity of a cilia-based mechanism for all vertebrates therefore has been questioned [3]. Here we show that a cilia-driven leftward flow precedes asymmetric nodal expression in the frog Xenopus. Motile monocilia emerged on the gastrocoel roof plate during neurulation and lengthened and polarized from an initially central position to the posterior pole of cells. Concomitantly, a robust leftward fluid flow developed from stage 15 onward, significantly before asymmetric nodal transcription started in the letlateral-plate mesoderm at stage 19. Injection of 1.5% methylcellulose into the archenteron prevented leftward flow and resulted in laterality defects, demonstrating that the flow itself was required for asymmetric gene expression and organ placement.