Cell surface fluctuations regulate early embryonic lineage sorting

Ayaka Yanagida; Elena Corujo-Simon; Christopher K Revell; Preeti Sahu; Giuliano G Stirparo; Irene M Aspalter; Alex K Winkel; Ruby Peters; Henry De Belly; Davide A D Cassani; Sarra Achouri; Raphael Blumenfeld; Kristian Franze; Edouard Hannezo; Ewa K Paluch; Jennifer Nichols; Kevin J Chalut

doi:10.1016/j.cell.2022.01.022

Cell surface fluctuations regulate early embryonic lineage sorting

Cell. 2022 Mar 3;185(5):777-793.e20. doi: 10.1016/j.cell.2022.01.022. Epub 2022 Feb 22.

Authors

Ayaka Yanagida¹, Elena Corujo-Simon², Christopher K Revell³, Preeti Sahu⁴, Giuliano G Stirparo², Irene M Aspalter⁵, Alex K Winkel⁶, Ruby Peters⁶, Henry De Belly⁷, Davide A D Cassani⁵, Sarra Achouri⁸, Raphael Blumenfeld⁹, Kristian Franze⁶, Edouard Hannezo⁴, Ewa K Paluch¹⁰, Jennifer Nichols¹¹, Kevin J Chalut¹²

Affiliations

¹ Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK; Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK; Living Systems Institute, University of Exeter, Exeter EX4 4QD, UK.
² Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK.
³ Cavendish Laboratory, Department of Physics, University of Cambridge, JJ Thomson Ave, Cambridge CB3 0HE, UK.
⁴ Institute of Science and Technology Austria, Am Campus 1, Klosterneuburg 3400, Austria.
⁵ MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
⁶ Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
⁷ Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK; MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
⁸ Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK; Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
⁹ Gonville & Caius College, University of Cambridge, Trinity St., Cambridge CB2 1TA, UK.
¹⁰ MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. Electronic address: ekp25@cam.ac.uk.
¹¹ Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK; Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. Electronic address: jenny.nichols@ed.ac.uk.
¹² Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. Electronic address: kc370@cam.ac.uk.

Abstract

In development, lineage segregation is coordinated in time and space. An important example is the mammalian inner cell mass, in which the primitive endoderm (PrE, founder of the yolk sac) physically segregates from the epiblast (EPI, founder of the fetus). While the molecular requirements have been well studied, the physical mechanisms determining spatial segregation between EPI and PrE remain elusive. Here, we investigate the mechanical basis of EPI and PrE sorting. We find that rather than the differences in static cell surface mechanical parameters as in classical sorting models, it is the differences in surface fluctuations that robustly ensure physical lineage sorting. These differential surface fluctuations systematically correlate with differential cellular fluidity, which we propose together constitute a non-equilibrium sorting mechanism for EPI and PrE lineages. By combining experiments and modeling, we identify cell surface dynamics as a key factor orchestrating the correct spatial segregation of the founder embryonic lineages.

Keywords: cell sorting; cell surface dynamics; cell surface mechanics; embryo development; lineage segregation; morphogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blastocyst* / metabolism
Cell Differentiation / physiology
Cell Lineage / physiology
Cell Membrane / metabolism
Embryo, Mammalian* / metabolism
Embryonic Development
Endoderm* / metabolism
Mammals
Mice
Protein Transport

Abstract

Publication types

MeSH terms

Grants and funding