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Embryo Size Regulates the Timing and Mechanism of Pluripotent Tissue Morphogenesis

Orietti, Lorenzo C. and Rosa, Viviane Souza and Antonica, Francesco and Kyprianou, Christos and Mansfield, William and Marques-Souza, Henrique and Shahbazi, Marta N. and Zernicka-Goetz, Magdalena (2021) Embryo Size Regulates the Timing and Mechanism of Pluripotent Tissue Morphogenesis. Stem Cell Reports, 16 (5). pp. 1182-1196. ISSN 2213-6711. PMCID PMC8185375. doi:10.1016/j.stemcr.2020.09.004.

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Mammalian embryogenesis is a paradigm of regulative development as mouse embryos show plasticity in the regulation of cell fate, cell number, and tissue morphogenesis. However, the mechanisms behind embryo plasticity remain largely unknown. Here, we determine how mouse embryos respond to an increase in cell numbers to regulate the timing and mechanism of embryonic morphogenesis, leading to the formation of the pro-amniotic cavity. Using embryos and embryonic stem cell aggregates of different size, we show that while pro-amniotic cavity formation in normal-sized embryos is achieved through basement membrane-induced polarization and exocytosis, cavity formation of increased-size embryos is delayed and achieved through apoptosis of cells that lack contact with the basement membrane. Importantly, blocking apoptosis, both genetically and pharmacologically, alters pro-amniotic cavity formation but does not affect size regulation in enlarged embryos. We conclude that the regulation of embryonic size and morphogenesis, albeit concomitant, have distinct molecular underpinnings.

Item Type:Article
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URLURL TypeDescription CentralArticle
Antonica, Francesco0000-0001-9359-9689
Kyprianou, Christos0000-0001-8516-9195
Marques-Souza, Henrique0000-0002-5008-8413
Shahbazi, Marta N.0000-0002-1599-5747
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2020 The Authors. This is an open access article under the CC BY license ( Received 4 June 2020, Revised 1 September 2020, Accepted 8 September 2020, Available online 8 October 2020. We acknowledge Neophytos Christodoulou, Bailey Weatherbee, and David Glover for discussion and feedback on the manuscript. L.C.O. was funded by a PhD fellowship from the Centre for Trophoblast Research, University of Cambridge. V.S.R. was supported by the CAPES (88881.132023/2016-01). F.A. was funded by an EMBO long-term fellowship. Work in the M.N.S. laboratory is funded by the European Molecular Laboratory (EMBO—Advanced EMBO fellowship) and the Medical Research Council (MC_UP_1201/24). Work in the M.Z.-G. laboratory is funded by a Wellcome Trust grant (207415/Z/17/Z), an ERC grant (669198), Open Philanthropy, Curci, and Weston Havens Foundations at Caltech. Author Contributions: L.C.O., V.S.R., M.N.S., and F.A. designed and performed the experiments with help from C.K. W.M. performed embryo transfer experiments. L.C.O., V.S.R., and M.N.S. analyzed the data. L.C.O., V.S.R., M.N.S., and M.Z.-G. wrote the paper. H.M.-S. supported the work of V.S.R. M.N.S. and M.Z.-G. supervised the study. M.Z.-G. conceived the project. Data and Code Availability: All relevant data are available from the corresponding authors upon reasonable request.
Funding AgencyGrant Number
University of CambridgeUNSPECIFIED
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)88881.132023/2016-01
European Molecular Biology Organization (EMBO)UNSPECIFIED
Medical Research Council (UK)MC_UP_1201/24
Wellcome Trust207415/Z/17/Z
European Research Council (ERC)669198
Open PhilanthropyUNSPECIFIED
Shurl and Kay Curci FoundationUNSPECIFIED
Weston Havens FoundationUNSPECIFIED
Subject Keywords:mouse embryogenesis; regulative development; lumenogenesis; apoptosis; size regulation; embryonic stem cells; morphogenesis; epithelial tissue; implantation; embryo
Issue or Number:5
PubMed Central ID:PMC8185375
Record Number:CaltechAUTHORS:20201009-083350141
Persistent URL:
Official Citation:Lorenzo C. Orietti, Viviane Souza Rosa, Francesco Antonica, Christos Kyprianou, William Mansfield, Henrique Marques-Souza, Marta N. Shahbazi, Magdalena Zernicka-Goetz, Embryo size regulates the timing and mechanism of pluripotent tissue morphogenesis, Stem Cell Reports, Volume 16, Issue 5, 2021, Pages 1182-1196, ISSN 2213-6711,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105945
Deposited By: Tony Diaz
Deposited On:09 Oct 2020 17:16
Last Modified:09 Feb 2022 19:47

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