期刊
CURRENT BIOLOGY
卷 26, 期 5, 页码 654-660出版社
CELL PRESS
DOI: 10.1016/j.cub.2015.12.071
关键词
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资金
- BBSRC [BB/F018940/1, G00661X, F021135]
- University of Edinburgh
- University of Nottingham
- Wellcome Trust Sanger Institute [WT098051]
- MRC [G0900740]
- NERC [R8/H10/56]
- Leverhulme Trust [F/00114U]
- G. Harold and Leila Y. Mathers Charitable Foundation
- Physical Science Oncology Center from the National Cancer Institute [U54CA143876]
- DFG [JA2108/1-1]
- JSPS
- Daiwa Foundation
- BBSRC
- Biotechnology and Biological Sciences Research Council [BB/F021135/1, BB/F018940/1, BB/G00661X/1, 1088483, BB/I023585/1] Funding Source: researchfish
- Medical Research Council [G0900740, MR/K001744/1] Funding Source: researchfish
- Natural Environment Research Council [NBAF010003] Funding Source: researchfish
- BBSRC [BB/I023585/1, BB/G00661X/1, BB/F018940/1, BB/F021135/1] Funding Source: UKRI
- MRC [G0900740, MR/K001744/1] Funding Source: UKRI
- NERC [NBAF010003] Funding Source: UKRI
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 [1, 2]. 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 existingmodels [3-5], 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 [6, 7], together these results are consistent with the view that animals with diverse body plans may derive their asymmetries from the same intracellular chiral elements [8].
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