The development of CRISPR for a mollusc establishes the formin Lsdia1 as the long-sought gene for snail dextral/sinistral coiling
The development of CRISPR for a mollusc establishes the formin Lsdia1 as the long-sought gene for snail dextral/sinistral coiling
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DOI：
10.1242/dev.175976
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发表时间：
2019-05-01
期刊：
影响因子：
4.6
通讯作者：
Kuroda, Reiko
中科院分区：
文献类型：
--
作者：
Abe, Masanori;Kuroda, Reiko
左右身体不对称的建立是一个关键的生物学过程，受到基因的严格调控。在CRISPR/Cas9对软体动物的首次应用中，我们果断地表明，肌动蛋白相关的透明基因Lsdia 1是决定淡水蜗牛Stagnalis壳卷曲方向的单一母体基因。该基因的双等位基因移码突变在完全右旋的遗传背景下产生了一代又一代左旋盘绕的后代。这是一个世纪以来一直在寻找的基因。我们还表明，该基因设置在一个细胞阶段的手性，最早观察到的破坏性的事件直接联系到身体的手性在动物王国。在第三次裂解时，细胞内手性被细胞间手性取代，导致不对称的nodal和Pitx表达，进而导致生物体手性。因此，我们的发现对无脊椎动物和脊椎动物（包括人类）的手性形成以及蜗牛手性的进化具有重要意义。
The establishment of left-right body asymmetry is a key biological process that is tightly regulated genetically. In the first application of CRISPR/Cas9 to a mollusc, we show decisively that the actin-related diaphanous gene Lsdia1 is the single maternal gene that determines the shell coiling direction of the freshwater snail Lymnaea stagnalis. Biallelic frameshift mutations of the gene produced sinistrally coiled offspring generation after generation, in the otherwise totally dextral genetic background. This is the gene sought for over a century. We also show that the gene sets the chirality at the one-cell stage, the earliest observed symmetry-breaking event linked directly to body handedness in the animal kingdom. The early intracellular chirality is superseded by the intercellular chirality during the 3rd cleavage, leading to asymmetric nodal and Pitx expression, and then to organismal body handedness. Thus, our findings have important implications for chiromorphogenesis in invertebrates as well as vertebrates, including humans, and for the evolution of snail chirality.This article has an associated 'The people behind the papers' interview.