Mitochondria-Derived H2O2 Promotes Symmetry Breaking of the C. elegans Zygote
De Henau, Sasha; Pagès-Gallego, Marc; Pannekoek, Willem-Jan; Dansen, Tobias B
(2020) Developmental Cell, volume 53, issue 3, pp. 263 - 271.e6
(Article)
Abstract
Symmetry breaking is an essential step in cell differentiation and early embryonic development. However, the molecular cues that trigger symmetry breaking remain largely unknown. Here, we show that mitochondrial H2O2 acts as a symmetry-breaking cue in the C. elegans zygote. We find that symmetry breaking is marked by a local
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H2O2 increase and coincides with a relocation of mitochondria to the cell cortex. Lowering endogenous H2O2 levels delays the onset of symmetry breaking, while artificially targeting mitochondria to the cellular cortex using a light-induced heterodimerization technique is sufficient to initiate symmetry breaking in a H2O2-dependent manner. In wild-type development, both sperm and maternal mitochondria contribute to symmetry breaking. Our findings reveal that mitochondrial H2O2-signaling promotes the onset of polarization, a fundamental process in development and cell differentiation, and this is achieved by both mitochondrial redistribution and differential H2O2-production.
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Keywords: C. elegans, H O, cell polarity, embryonic development, mitochondria, redox signaling, symmetry breaking, Cell Polarity, Body Patterning/drug effects, Hydrogen Peroxide/pharmacology, Oxidants/pharmacology, Mitochondria/metabolism, Caenorhabditis elegans/drug effects, Animals, Zygote/cytology, Embryo, Nonmammalian/cytology, Caenorhabditis elegans Proteins/genetics, General Biochemistry,Genetics and Molecular Biology, Molecular Biology, Cell Biology, Developmental Biology, Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural
ISSN: 1534-5807
Publisher: Cell Press
Note: Funding Information: We thank our Molecular Cancer Research lab members for helpful discussions. We are grateful to Loes van Dam and Matthijs Baars (UMC Utrecht); Sander van den Heuvel, Mike Boxem, Lars Eric Fielmich, Ruben Schmidt, Vincent Portegijs, and Martin Harterink (University Utrecht); Bart Braeckman and Caroline Vlaeminck (Ghent University); Erik Griffin and Xintao Fan (Dartmouth College); Tobias Dick and Koen Van Laer (German Cancer Research Center); and Daniel Dickinson (UT Austin) for strains, reagents, and expertise. We also thank Mike Boxem and Boudewijn Burgering for helpful comments on the manuscript. S.D.H. is supported by NWO grant 016.Veni.181.051 , and T.B.D. is supported by KWF grant UU 2014-6902 . Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs ( P40 OD010440 ). The data generated or analyzed during this study are included in this article and its supplementary materials. Funding Information: We thank our Molecular Cancer Research lab members for helpful discussions. We are grateful to Loes van Dam and Matthijs Baars (UMC Utrecht); Sander van den Heuvel, Mike Boxem, Lars Eric Fielmich, Ruben Schmidt, Vincent Portegijs, and Martin Harterink (University Utrecht); Bart Braeckman and Caroline Vlaeminck (Ghent University); Erik Griffin and Xintao Fan (Dartmouth College); Tobias Dick and Koen Van Laer (German Cancer Research Center); and Daniel Dickinson (UT Austin) for strains, reagents, and expertise. We also thank Mike Boxem and Boudewijn Burgering for helpful comments on the manuscript. S.D.H. is supported by NWO grant 016.Veni.181.051, and T.B.D. is supported by KWF grant UU 2014-6902. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). The data generated or analyzed during this study are included in this article and its supplementary materials. S.D.H. and T.B.D. designed the experiments and wrote the paper. S.D.H. conducted the experiments. S.D.H. M.P.-G, and W.-J.P. analyzed the data. The authors declare no competing interests. Funding Information: C. elegans strains were maintained according to standard procedures ( Brenner, 1974 ). C. elegans strains were cultured on plates containing nematode growth medium seeded with OP50 Escherichia coli bacteria. All strains were kept at 23°C when used for experiments, except when noted otherwise. Standard crosses were done to generate some of the lines used in this study. All strains used in this study are listed in the Key Resources Table . Some strains were provided by the Caenorhabditis Genetics Center funded by the National Institutes of Health National Center for Research Resources. Publisher Copyright: © 2020 Elsevier Inc.
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