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Coordination Between Embryo Growth and Trophoblast Migration Upon Implantation Delineates Mouse Embryogenesis

View ORCID ProfileV. Bondarenko, View ORCID ProfileM. Nikolaev, View ORCID ProfileD. Kromm, View ORCID ProfileR. Belousov, View ORCID ProfileA. Wolny, View ORCID ProfileS. Rezakhani, View ORCID ProfileJ. Hugger, View ORCID ProfileV. Uhlmann, L. Hufnagel, View ORCID ProfileA. Kreshuk, View ORCID ProfileJ. Ellenberg, View ORCID ProfileA. Erzberger, M. Lutolf, View ORCID ProfileT. Hiiragi
doi: https://doi.org/10.1101/2022.06.13.495767
V. Bondarenko
1European Molecular Biology Laboratory, Developmental Biology Unit, 69117 Heidelberg, Germany
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M. Nikolaev
4Integrative Biosciences Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Building AA-B 039, CH-1015 Lausanne, Switzerland
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D. Kromm
2European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany
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R. Belousov
2European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany
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A. Wolny
2European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany
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S. Rezakhani
4Integrative Biosciences Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Building AA-B 039, CH-1015 Lausanne, Switzerland
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J. Hugger
2European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany
3EMBL-EBI, Wellcome Genome Campus, Hinxton, CB10 1SD, UK
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V. Uhlmann
3EMBL-EBI, Wellcome Genome Campus, Hinxton, CB10 1SD, UK
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L. Hufnagel
2European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany
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A. Kreshuk
2European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany
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J. Ellenberg
2European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany
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A. Erzberger
2European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany
6Department of Physics and Astronomy, Heidelberg University, 69120 Heidelberg, Germany
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  • For correspondence: anna.erzberger@embl.de matthias.lutolf@epfl.ch t.hiiragi@hubrecht.eu
M. Lutolf
4Integrative Biosciences Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Building AA-B 039, CH-1015 Lausanne, Switzerland
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  • For correspondence: anna.erzberger@embl.de matthias.lutolf@epfl.ch t.hiiragi@hubrecht.eu
T. Hiiragi
1European Molecular Biology Laboratory, Developmental Biology Unit, 69117 Heidelberg, Germany
5Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, 606-8501, Japan
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  • For correspondence: anna.erzberger@embl.de matthias.lutolf@epfl.ch t.hiiragi@hubrecht.eu
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SUMMARY

Implantation marks a key transition in mammalian development. The role of embryo-uterus interaction in periimplantation development is however poorly understood due to inaccessibility in utero. Here, we develop an engineered uterus-like microenvironment to recapitulate mouse development ex vivo up to E5.25 and discover an essential role of integrin-mediated trophoblast adhesion to the uterine matrix. Light-sheet microscopy shows that trophoblast cells undergo Rac1-dependent collective migration upon implantation, displacing Reichert’s membrane and generating space for egg cylinder growth. The key role of coordination between trophoblast migration and embryo growth is verified by experimentally manipulating the migration velocity and geometry of the engineered uterus. Modeling the implanting embryo as a wetting droplet links the tissue shape dynamics to underlying changes in trophoblast adhesion and suggests that the corresponding tension release facilitates egg cylinder formation. Together, this study provides mechanisms by which dynamic embryo-uterus interactions play an essential role in peri-implantation development.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/kreshuklab/mouse-embryo-seg

  • https://doi.org/10.5281/zenodo.6546550

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 16, 2022.
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Coordination Between Embryo Growth and Trophoblast Migration Upon Implantation Delineates Mouse Embryogenesis
V. Bondarenko, M. Nikolaev, D. Kromm, R. Belousov, A. Wolny, S. Rezakhani, J. Hugger, V. Uhlmann, L. Hufnagel, A. Kreshuk, J. Ellenberg, A. Erzberger, M. Lutolf, T. Hiiragi
bioRxiv 2022.06.13.495767; doi: https://doi.org/10.1101/2022.06.13.495767
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Coordination Between Embryo Growth and Trophoblast Migration Upon Implantation Delineates Mouse Embryogenesis
V. Bondarenko, M. Nikolaev, D. Kromm, R. Belousov, A. Wolny, S. Rezakhani, J. Hugger, V. Uhlmann, L. Hufnagel, A. Kreshuk, J. Ellenberg, A. Erzberger, M. Lutolf, T. Hiiragi
bioRxiv 2022.06.13.495767; doi: https://doi.org/10.1101/2022.06.13.495767

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