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

Molè, Matteo Amitaba and Weberling, Antonia and Fässler, Reinhard and Campbell, Alison and Fishel, Simon and Zernicka-Goetz, Magdalena (2021) Integrin β1 coordinates survival and morphogenesis of the embryonic lineage upon implantation and pluripotency transition. Cell Reports, 34 (10). Art. No. 108834. ISSN 2211-1247. PMCID PMC7966855. doi:10.1016/j.celrep.2021.108834. https://resolver.caltech.edu/CaltechAUTHORS:20210310-141520229

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.celrep.2021.108834DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966855PubMed CentralArticle
ORCID:
AuthorORCID
Molè, Matteo Amitaba0000-0001-7342-4849
Weberling, Antonia0000-0001-8282-5695
Zernicka-Goetz, Magdalena0000-0002-7004-2471
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.
Funders:
Funding AgencyGrant Number
Wellcome Trust207415/Z/17/Z
European Research Council (ERC)669198
Marie Curie Fellowship721537
NIHR01 HD100456-01A1
NIHDP1 HD104575-01
Open PhilanthropyUNSPECIFIED
Silicon Valley Community FoundationUNSPECIFIED
Weston Havens FoundationUNSPECIFIED
Shurl and Kay Curci FoundationUNSPECIFIED
Subject Keywords:epiblast; morphogenesis; integrins; survival; apoptosis; actomyosin; mouse embryo; human embryo
Issue or Number:10
PubMed Central ID:PMC7966855
DOI:10.1016/j.celrep.2021.108834
Record Number:CaltechAUTHORS:20210310-141520229
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210310-141520229
Official Citation:Matteo Amitaba Molè, Antonia Weberling, Reinhard Fässler, Alison Campbell, Simon Fishel, Magdalena Zernicka-Goetz, Integrin β1 coordinates survival and morphogenesis of the embryonic lineage upon implantation and pluripotency transition, Cell Reports, Volume 34, Issue 10, 2021, 108834, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2021.108834. (https://www.sciencedirect.com/science/article/pii/S2211124721001480)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108388
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:10 Mar 2021 22:27
Last Modified:19 Apr 2021 18:00

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