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Published March 9, 2021 | Supplemental Material + Published
Journal Article Open

Integrin β1 coordinates survival and morphogenesis of the embryonic lineage upon implantation and pluripotency transition

Abstract

At implantation, the embryo establishes contacts with the maternal endometrium. This stage is associated with a high incidence of preclinical pregnancy losses. While the maternal factors underlying uterine receptivity have been investigated, the signals required by the embryo for successful peri-implantation development remain elusive. To explore these, we studied integrin β1 signaling, as embryos deficient for this receptor degenerate at implantation. We demonstrate that the coordinated action of pro-survival signals and localized actomyosin suppression via integrin β1 permits the development of the embryo beyond implantation. Failure of either process leads to developmental arrest and apoptosis. Pharmacological stimulation through fibroblast growth factor 2 (FGF2) and insulin-like growth factor 1 (IGF1), coupled with ROCK-mediated actomyosin inhibition, rescues the deficiency of integrin β1, promoting progression to post-implantation stages. Mutual exclusion between integrin β1 and actomyosin seems to be conserved in the human embryo, suggesting the possibility that these mechanisms could also underlie the transition of the human epiblast from pre- to post-implantation.

Additional Information

© 2021 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Received 12 May 2020, Revised 30 November 2020, Accepted 17 February 2021, Available online 9 March 2021. We thank all of the members of the M.Z.-G. lab for critical discussion. We are grateful to all of the patients for donating their embryos and embryologists at the CARE clinics for help and support. We thank Marta N. Shahbazi for her help in thawing the human embryos. We thank William Mansfield for the support with mouse embryos transfers. Work in the M.Z.-G. laboratory is supported by grants from the Wellcome Trust (207415/Z/17/Z); the ERC (grant no. 669198); EU Horizon 2020 Marie Skłodowska-Curie actions (ImageInLife, 721537); the NIH (R01 HD100456-01A1); the NIH Pioneer Award Fund (DP1 HD104575-01); the Open Philanthropy/Silicon Valley Community Foundation; the Weston Havens Foundation; and the Shurl and Kay Curci Foundation, to M.Z.-G. Author contributions: M.A.M. and M.Z.-G. conceptualized and designed the project. M.A.M. and A.W. performed and analyzed the experiments regarding mESCs and mouse embryos. M.A.M. carried out the experiments regarding human embryos. A.W. and M.A.M. prepared the illustrations. A.C. and S.F. oversaw and provided human embryos for these studies. R.F. provided the conditional integrin β1 mouse line. M.Z.-G. supervised the project. M.A.M. wrote the manuscript with the help of M.Z.-G. The authors declare no competing interests.

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Supplemental Material - 1-s2.0-S2211124721001480-mmc1.pdf

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Additional details

Created:
August 22, 2023
Modified:
December 22, 2023