Actomyosin polarisation through PLC-PKC triggers symmetry breaking of the mouse embryo
Abstract
Establishment of cell polarity in the mammalian embryo is fundamental for the first cell fate decision that sets aside progenitor cells for both the new organism and the placenta. Yet the sequence of events and molecular mechanism that trigger this process remain unknown. Here, we show that de novo polarisation of the mouse embryo occurs in two distinct phases at the 8-cell stage. In the first phase, an apical actomyosin network is formed. This is a pre-requisite for the second phase, in which the Par complex localises to the apical domain, excluding actomyosin and forming a mature apical cap. Using a variety of approaches, we also show that phospholipase C-mediated PIP_2 hydrolysis is necessary and sufficient to trigger the polarisation of actomyosin through the Rho-mediated recruitment of myosin II to the apical cortex. Together, these results reveal the molecular framework that triggers de novo polarisation of the mouse embryo.
Additional Information
© The Author(s) 2017. Open Access - This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received: 20 February 2017. Accepted: 9 August 2017. Published 13 October 2017. We thank all colleagues in our lab and D. Glover for the very helpful suggestions on the manuscript. This work was supported by the Wellcome Trust. M.Z.G. is a Wellcome Trust Senior Research Fellow, M.Z. is supported by the Cambridge Trust, and M.N.S. is an EMBO Postdoctoral Fellow. We would like to dedicate this work to M. Johnson, a pioneer of cell polarisation studies. Author Contributions: M.Z. designed and conducted experiments, analysed and interpreted the data with the help of all co-authors. C.Y.L. performed pilot experiments. M.N.S. discussed and helped to interpret the data. M.Z.-G. conceived and supervised the project, and helped to interpret the data. The manuscript was written by M.Z., M.N.S. and M.Z.-G. The authors declare no competing financial interests.Attached Files
Published - s41467-017-00977-8.pdf
Supplemental Material - 41467_2017_977_MOESM1_ESM.pdf
Supplemental Material - 41467_2017_977_MOESM2_ESM.pdf
Supplemental Material - 41467_2017_977_MOESM3_ESM.pdf
Supplemental Material - 41467_2017_977_MOESM4_ESM.mov
Supplemental Material - 41467_2017_977_MOESM5_ESM.mov
Supplemental Material - 41467_2017_977_MOESM6_ESM.avi
Supplemental Material - 41467_2017_977_MOESM7_ESM.avi
Supplemental Material - 41467_2017_977_MOESM8_ESM.avi
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Additional details
- PMCID
- PMC5640629
- Eprint ID
- 94531
- Resolver ID
- CaltechAUTHORS:20190405-170314469
- Wellcome Trust
- Cambridge Trust
- European Molecular Biology Organization (EMBO)
- Created
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2019-04-09Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field