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Basement membrane remodelling regulates mouse embryogenesis

Kyprianou, Christos and Christodoulou, Neophytos and Hamilton, Russell S. and Nahaboo, Wallis and Boomgaard, Diana Suarez and Amadei, Gianluca and Migeotte, Isabelle and Zernicka-Goetz, Magdalena (2020) Basement membrane remodelling regulates mouse embryogenesis. Nature, 582 (7811). pp. 253-258. ISSN 0028-0836. https://resolver.caltech.edu/CaltechAUTHORS:20200121-134023730

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Abstract

Tissue sculpting during development has been attributed mainly to cellular events through processes such as convergent extension or apical constriction. However, recent work has revealed roles for basement membrane remodelling in global tissue morphogenesis. Upon implantation, the epiblast and extraembryonic ectoderm of the mouse embryo become enveloped by a basement membrane. Signalling between the basement membrane and these tissues is critical for cell polarization and the ensuing morphogenesis. However, the mechanical role of the basement membrane in post-implantation embryogenesis remains unknown. Here we demonstrate the importance of spatiotemporally regulated basement membrane remodelling during early embryonic development. Specifically, we show that Nodal signalling directs the generation and dynamic distribution of perforations in the basement membrane by regulating the expression of matrix metalloproteinases. This basement membrane remodelling facilitates embryo growth before gastrulation. The establishment of the anterior–posterior axis further regulates basement membrane remodelling by localizing Nodal signalling—and therefore the activity of matrix metalloproteinases and basement membrane perforations—to the posterior side of the embryo. Perforations on the posterior side are essential for primitive-streak extension during gastrulation by rendering the basement membrane of the prospective primitive streak more prone to breaching. Thus spatiotemporally regulated basement membrane remodelling contributes to the coordination of embryo growth, morphogenesis and gastrulation.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41586-020-2264-2DOIArticle
https://rdcu.be/b3ZvzPublisherFree ReadCube access
https://github.com/darogan/Kyprianou_Zernika-GoetzRelated ItemCode
https://doi.org/10.5281/zenodo.3610335DOICode
ORCID:
AuthorORCID
Kyprianou, Christos0000-0001-8516-9195
Christodoulou, Neophytos0000-0003-4338-5847
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2020 Springer Nature Limited. Received 14 March 2019; Accepted 05 March 2020; Published 06 May 2020. We thank D. Glover, M. Shahbazi and M. Zhu for valuable discussions; A. Cox for drawing the model in Fig. 4i; M. Kuehn for the Nodalfl/fl mice and V. Kouskoff for the T-GFP mice. D.S.B. is supported by the FNRS; W.N. is supported by WELBIO; I.M. is a FNRS research associate and an investigator of WELBIO. The M.Z.-G. laboratory is supported by grants from the European Research Council (669198) and the Wellcome Trust (098287/Z/12/Z). Data availability: The source data used in all graphs are provided in the Source Data files. Raw image files are available from the corresponding author upon request. Code availability: The codes used in this study are available at https://github.com/darogan/Kyprianou_Zernika-Goetz and https://doi.org/10.5281/zenodo.3610335. Author Contributions: C.K. and N.C. designed and carried out the experiments and data analysis. R.S.H. performed the bioinformatics analysis. G.A. performed the RNA in situ experiments. W.N., D.S.B. and I.M. generated the Ttr-cre;Rhoafl/− embryos. M.Z.-G., C.K. and N.C. conceived the study and wrote the manuscript. M.Z.-G. supervised the study. The authors declare no competing interests.
Group:Tianqiao and Chrissy Chen Institute for Neuroscience
Funders:
Funding AgencyGrant Number
Fonds de la Recherche Scientifique (FNRS)UNSPECIFIED
Walloon Excellence in Lifesciences and Biotechnology (WELBIO)UNSPECIFIED
European Research Council (ERC)669198
Wellcome Trust098287/Z/12/Z
Subject Keywords:Embryology; Morphogenesis
Issue or Number:7811
Record Number:CaltechAUTHORS:20200121-134023730
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200121-134023730
Official Citation:Kyprianou, C., Christodoulou, N., Hamilton, R.S. et al. Basement membrane remodelling regulates mouse embryogenesis. Nature 582, 253–258 (2020). https://doi.org/10.1038/s41586-020-2264-2
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:100818
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:27 Apr 2020 18:30
Last Modified:12 Jun 2020 16:40

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