Formin Is Associated with Left-Right Asymmetry in the Pond Snail and the Frog.
Formin Is Associated with Left-Right Asymmetry in the Pond Snail and the Frog.
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DOI：
10.1016/j.cub.2015.12.071
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发表时间：
2016-03-07
期刊：
影响因子：
--
通讯作者：
Blaxter ML
中科院分区：
文献类型：
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作者：
Davison A;McDowell GS;Holden JM;Johnson HF;Koutsovoulos GD;Liu MM;Hulpiau P;Van Roy F;Wade CM;Banerjee R;Yang F;Chiba S;Davey JW;Jackson DJ;Levin M;Blaxter ML
虽然在从脊椎动物到果蝇的多种动物中已经鉴定出建立左右不对称性的途径的组成部分，但令人惊讶的是，在最明显的手性动物腹足类蜗牛中，参与第一个对称性破坏步骤的基因仍然完全未知。此前，对蜗牛的研究表明，对称性破缺下游节点的左右信号传导可能是双边对称动物的祖先特征。在这里，我们报告了串联复制的透明相关福明的一个副本中的失能突变与池塘蜗牛的对称性破缺完全相关。抗福尔明药物治疗将右旋蜗牛胚胎转化为左旋表型，并且在青蛙中，通过显微注射福尔明进行药物抑制或过度表达对早期（纤毛前）胚胎具有手性随机效应，这一观察结果支持了这一点。与基于现有模型的预期相反，我们发现 2 细胞和 4 细胞蜗牛胚胎中存在不对称基因表达，先于形态不对称。由于福尔马林-肌动蛋白丝已被证明是体外不对称性破坏开关的一部分，因此这些结果与具有不同身体结构的动物可能从相同的细胞内手性元素衍生其不对称性的观点是一致的。动物往往外表对称，但内部不对称。与其他动物不同，蜗牛表现出遗传性的不对称变异。我们发现蜗牛和青蛙都使用共同的基因来定义左右不对称。不对称可能是细胞和动物的一种古老且保守的特性。在蜗牛和青蛙中发现了一种细胞支架蛋白，它可以控制身体的不对称性，无论是蜗牛壳卷曲的方向，还是青蛙心脏向左还是向右。动物（包括人类）的身体不对称可能源于细胞高度保守的内在不对称性。
While components of the pathway that establishes left-right asymmetry have been identified in diverse animals, from vertebrates to flies, it is striking that the genes involved in the first symmetry-breaking step remain wholly unknown in the most obviously chiral animals, the gastropod snails. Previously, research on snails was used to show that left-right signaling of Nodal, downstream of symmetry breaking, may be an ancestral feature of the Bilateria. Here, we report that a disabling mutation in one copy of a tandemly duplicated, diaphanous-related formin is perfectly associated with symmetry breaking in the pond snail. This is supported by the observation that an anti-formin drug treatment converts dextral snail embryos to a sinistral phenocopy, and in frogs, drug inhibition or overexpression by microinjection of formin has a chirality-randomizing effect in early (pre-cilia) embryos. Contrary to expectations based on existing models, we discovered asymmetric gene expression in 2- and 4-cell snail embryos, preceding morphological asymmetry. As the formin-actin filament has been shown to be part of an asymmetry-breaking switch in vitro, together these results are consistent with the view that animals with diverse body plans may derive their asymmetries from the same intracellular chiral elements. Animals tend to be outwardly symmetric but internally are asymmetric Unlike other animals, snails show inherited variation in asymmetry We found that both snails and frogs use a common gene to define left and right Asymmetry is probably an ancient and conserved property of cells and animals Davison et al. have discovered a cell scaffolding protein in snails and frogs that controls body asymmetry, either the direction a snail shell coils, or whether a frog heart is placed to the left or right. Body asymmetry in animals, including humans, likely arises from a highly conserved, intrinsic asymmetry of the cell.