Chiral blastomere arrangement dictates zygotic left-right asymmetry pathway in snails
Chiral blastomere arrangement dictates zygotic left-right asymmetry pathway in snails
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DOI：
10.1038/nature08597
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发表时间：
2009-12-10
期刊：
影响因子：
64.8
通讯作者：
Shimizu, Miho
中科院分区：
文献类型：
--
作者：
Kuroda, Reiko;Endo, Bunshiro;Shimizu, Miho
大多数动物表现出内部和/或外部左右不对称。已经针对脊椎动物（1-10）和无脊椎动物（1,2,4,9,11-14）提出了几种确定左右不对称性的机制，但它们仍然没有得到很好的表征，特别是在早期发育阶段。腹足动物 Lymnaea stagnalis 和密切相关的 Lymnaea peregra 在一个物种内同时具有左旋（隐性）和右旋（显性）蜗牛，并且手性是遗传性的，由具有母性功能的单个基因座决定 (15-18)。有趣的是，决定用手习惯的基因和机制尚未确定。在这里，我们表明，在 L. stagnalis 中，八细胞阶段（但不是两细胞或四细胞阶段）的手性卵裂球排列决定了整个发育程序的左右不对称性，并在 Nodal 信号通路的上游发挥作用。因此，我们可以证明第三次分裂手性（从四细胞阶段到八细胞阶段）的机械显微操作会导致胚胎用手性的逆转。这些经过操纵的胚胎发育成“右旋”左旋和“左旋”右旋蜗牛，即正常健康的可育生物体，其所有常见的左右不对称性都与母亲遗传信息编码的不对称性相反。此外，操作逆转了胚胎节点的表达模式。使用回交的 F-7 同类动物，我们可以证明手性决定基因与第三次卵裂时促进显性型卵裂球排列的手性细胞骨架动力学之间存在强大的遗传联系。这些结果证实了八细胞阶段母体决定的卵裂球排列在决定生物体手性发生中合子信号通路中的至关重要性。类似的手性卵裂球配置机制也可能在后口动物/脊椎动物的左右模式中的节点通路上游起作用。
Most animals display internal and/or external left-right asymmetry. Several mechanisms for left-right asymmetry determination have been proposed for vertebrates(1-10) and invertebrates(1,2,4,9,11-14) but they are still not well characterized, particularly at the early developmental stage. The gastropods Lymnaea stagnalis and the closely related Lymnaea peregra have both the sinistral (recessive) and the dextral (dominant) snails within a species and the chirality is hereditary, determined by a single locus that functions maternally(15-18). Intriguingly, the handedness-determining gene(s) and the mechanisms are not yet identified. Here we show that in L. stagnalis, the chiral blastomere arrangement at the eight-cell stage (but not the two-or four-cell stage) determines the left-right asymmetry throughout the developmental programme, and acts upstream of the Nodal signalling pathway. Thus, we could demonstrate that mechanical micromanipulation of the third cleavage chirality (from the four-to the eight-cell stage) leads to reversal of embryonic handedness. These manipulated embryos grew to 'dextralized' sinistral and 'sinistralized' dextral snails-that is, normal healthy fertile organisms with all the usual left-right asymmetries reversed to that encoded by the mothers' genetic information. Moreover, manipulation reversed the embryonic nodal expression patterns. Using backcrossed F-7 congenic animals, we could demonstrate a strong genetic linkage between the handedness-determining gene( s) and the chiral cytoskeletal dynamics at the third cleavage that promotes the dominant-type blastomere arrangement. These results establish the crucial importance of the maternally determined blastomere arrangement at the eight-cell stage in dictating zygotic signalling pathways in the organismal chiromorphogenesis. Similar chiral blastomere configuration mechanisms may also operate upstream of the Nodal pathway in left-right patterning of deuterostomes/vertebrates.