Marangoni-like tissue flows enhance symmetry breaking of embryonic organoids
During early development of multi-cellular animals, cells self-organize to set up the body axes, such as the primary head-to-tail axis, based on which the later body plan is defined. Several signaling pathways are known to control body axis formation. Here, we show, however, that also tissue mechani...
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11.03.2025
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| Abstract | During early development of multi-cellular animals, cells self-organize to set up the body axes, such as the primary head-to-tail axis, based on which the later body plan is defined. Several signaling pathways are known to control body axis formation. Here, we show, however, that also tissue mechanics plays an important role during this process. We focus on the emergence of a primary axis in initially spherical aggregates of mouse embryonic stem cells, which mirrors events in the early mouse embryo. These aggregates break rotational symmetry to establish an axial organization with domains of different expression profiles, e.g. of the transcription factor T/Bra and the adhesion molecule E-cadherin. Combining quantitative microscopy and physical modeling, we identify large-scale tissue flows with a recirculation component and demonstrate that they significantly contribute to symmetry breaking. We show that the recirculating flows are explained by a difference in tissue surface tension across domains, akin to Marangoni flows, which we further confirm by aggregate fusion experiments. Our work highlights that body axis formation is not only driven by biochemical processes, but that it can also be amplified by tissue flows. We expect that this type of amplification may operate in many other organoid and in-vivo systems. |
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| AbstractList | During early development of multi-cellular animals, cells self-organize to set up the body axes, such as the primary head-to-tail axis, based on which the later body plan is defined. Several signaling pathways are known to control body axis formation. Here, we show, however, that also tissue mechanics plays an important role during this process. We focus on the emergence of a primary axis in initially spherical aggregates of mouse embryonic stem cells, which mirrors events in the early mouse embryo. These aggregates break rotational symmetry to establish an axial organization with domains of different expression profiles, e.g. of the transcription factor T/Bra and the adhesion molecule E-cadherin. Combining quantitative microscopy and physical modeling, we identify large-scale tissue flows with a recirculation component and demonstrate that they significantly contribute to symmetry breaking. We show that the recirculating flows are explained by a difference in tissue surface tension across domains, akin to Marangoni flows, which we further confirm by aggregate fusion experiments. Our work highlights that body axis formation is not only driven by biochemical processes, but that it can also be amplified by tissue flows. We expect that this type of amplification may operate in many other organoid and in-vivo systems. |
| Author | Merkel, Matthias Gsell, Simon Lenne, Pierre-François Tlili, Sham |
| Author_xml | – sequence: 1 givenname: Simon orcidid: 0000-0003-4195-7792 surname: Gsell fullname: Gsell, Simon email: simon.gsell@univ-amu.fr organization: Aix Marseille Univ, CNRS, Centrale Med, IRPHE (UMR 7342), Turing Centre for Living Systems – sequence: 2 givenname: Sham orcidid: 0000-0001-6018-9923 surname: Tlili fullname: Tlili, Sham organization: Aix Marseille Univ, CNRS, IBDM (UMR 7288), Turing Centre for Living systems – sequence: 3 givenname: Matthias orcidid: 0000-0001-9118-1270 surname: Merkel fullname: Merkel, Matthias organization: Aix Marseille Univ, Université de Toulon, CNRS, CPT (UMR 7332), Turing Centre for Living systems – sequence: 4 givenname: Pierre-François orcidid: 0000-0003-1066-7506 surname: Lenne fullname: Lenne, Pierre-François organization: Aix Marseille Univ, CNRS, IBDM (UMR 7288), Turing Centre for Living systems |
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| Cites_doi | 10.1101/2023.01.27.525895 10.1038/s41586-020-2024-3 10.1016/j.stem.2023.04.018 10.1101/2022.08.01.502159 |
| ContentType | Paper |
| Copyright | 2024, Posted by Cold Spring Harbor Laboratory |
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| DOI | 10.1101/2023.09.22.559003 |
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| Notes | Competing Interest Statement: The authors have declared no competing interest. |
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| References | Mongera, Rowghanian, Gustafson, Shelton, Kealhofer, Carn, Serwane, Lucio, Giammona, Campàs (2023.09.22.559003v2.54) 2018; 561 Townes, Holtfreter (2023.09.22.559003v2.42) 1955; 128 de Jong, Adegeest, Bérenger-Currias, Mircea, Merks, Semrau (2023.09.22.559003v2.47) 2023 van den Brink, Baillie-Johnson, Balayo, Hadjantonakis, Nowotschin, Turner, Martinez Arias (2023.09.22.559003v2.6) 2014; 141 Beccari, Moris, Girgin, Turner, Baillie-Johnson, Cossy, Lutolf, Duboule, Arias (2023.09.22.559003v2.7) 2018; 562 Manning, Foty, Steinberg, Schoetz (2023.09.22.559003v2.45) 2010; 107 Stirbat, Mgharbel, Bodennec, Ferri, Mertani, Rieu, Delanoë-Ayari (2023.09.22.559003v2.50) 2013; 8 van den Brink, Alemany, van Batenburg, Moris, Blotenburg, Vivié, Baillie-Johnson, Nichols, Sonnen, Martinez Arias, van Oudenaarden (2023.09.22.559003v2.8) 2020 Underhill, Toettcher (2023.09.22.559003v2.27) 2023 Harris (2023.09.22.559003v2.44) 1976; 61 Flenner, Janosi, Barz, Neagu, Forgacs, Kosztin (2023.09.22.559003v2.38) 2012; 85 Oriola, Marin-Riera, Anlaş, Gritti, Sanaki-Matsumiya, Aalderink, Ebisuya, Sharpe, Trivedi (2023.09.22.559003v2.39) 2022; 18 Saadaoui, Rocancourt, Roussel, Corson, Gros (2023.09.22.559003v2.24) 2020; 367 Dominguez, Krup, Muncie, Bruneau (2023.09.22.559003v2.3) 2022 Turner, Girgin, Alonso-Crisostomo, Trivedi, Baillie-Johnson, Glodowski, Hayward, Collignon, Gustavsen, Serup (2023.09.22.559003v2.26) 2017; 144 Rozbicki, Chuai, Karjalainen, Song, Sang, Martin, Knölker, Macdonald, Weijer (2023.09.22.559003v2.19) 2015; 17 Tlili, Yin, Rupprecht, Mendieta-Serrano, Weissbart, Verma, Teng, Toyama, Prost, Saunders (2023.09.22.559003v2.22) 2019; 116 Rossi, Broguiere, Miyamoto, Boni, Guiet, Girgin, Kelly, Kwon, Lutolf (2023.09.22.559003v2.15) 2021; 28 van den Brink, Alemany, van Batenburg, Moris, Blotenburg, Vivie, Baillie-Johnson, Nichols, Sonnen, Martinez Arias (2023.09.22.559003v2.12) 2020; 582 Veenvliet, Bolondi, Kretzmer, Haut, Scholze-Wittler, Schifferl, Koch, Guignard, Kumar, Pustet (2023.09.22.559003v2.13) 2020; 370 Maitre, Berthoumieux, Krens, Salbreux, Julicher, Paluch, Heisenberg (2023.09.22.559003v2.32) 2012; 338 Steinberg (2023.09.22.559003v2.43) 1963; 141 Ibrahimi, Merkel (2023.09.22.559003v2.51) 2023; 25 Gsell, D’Ortona, Favier (2023.09.22.559003v2.36) 2021; 429 Gsell, Merkel (2023.09.22.559003v2.48) 2022; 18 van den Brink, van Oudenaarden (2023.09.22.559003v2.11) 2021; 31 Gehrels, Chakrabortty, Perrin, Merkel, Lecuit (2023.09.22.559003v2.21) 2023; 120 Schötz, Burdine, Jülicher, Steinberg, Heisenberg, Foty (2023.09.22.559003v2.49) 2008; 2 Cachat, Liu, Martin, Yuan, Yin, Hohenstein, Davies (2023.09.22.559003v2.33) 2016; 6 Moris, Martinez Arias, Steventon (2023.09.22.559003v2.10) 2020; 64 Williams, Solnica-Krezel (2023.09.22.559003v2.53) 2020; 9 Foty, Steinberg (2023.09.22.559003v2.30) 2005; 278 Schmitt, Stark (2023.09.22.559003v2.40) 2016; 28 Saykali, Mathiah, Nahaboo, Racu, Hammou, Defrance, Migeotte (2023.09.22.559003v2.5) 2019; 8 Saadaoui, Rocancourt, Roussel, Corson, Gros (2023.09.22.559003v2.20) 2020; 367 Steinberg (2023.09.22.559003v2.29) 1963; 141 Amack, Manning (2023.09.22.559003v2.31) 2012; 338 McDole, Guignard, Amat, Berger, Malandain, Royer, Turaga, Branson, Keller (2023.09.22.559003v2.4) 2018; 175 Gsell, D’Ortona, Favier (2023.09.22.559003v2.35) 2020; 101 Velarde, Zeytounian, Velarde, Sayir, Schneider, Schrefler, Bianchi, Tasso (2023.09.22.559003v2.37) 2002; 428 Fulton, Trivedi, Attardi, Anlas, Dingare, Arias, Steventon (2023.09.22.559003v2.52) 2020; 30 Yadav, Yousafzai, Amiri, Style, Dufresne, Murrell (2023.09.22.559003v2.55) 2022; 7 Moris, Anlas, van den Brink, Alemany, Schröder, Ghimire, Balayo, van Oudenaarden, Martinez Arias (2023.09.22.559003v2.9) 2020; 582 Tiribocchi, Wittkowski, Marenduzzo, Cates (2023.09.22.559003v2.34) 2015; 115 Etournay, Popović, Merkel, Nandi, Blasse, Aigouy, Brandl, Myers, Salbreux, Jülicher, Eaton (2023.09.22.559003v2.18) 2015; 4 Bao, Cornwall-Scoones, Sanchez-Vasquez, Cox, Chen, De Jonghe, Shadkhoo, Hollfelder, Thomson, Glover (2023.09.22.559003v2.46) 2022; 24 Lucas, Kanade (2023.09.22.559003v2.28) 1981 Holtfreter (2023.09.22.559003v2.41) 1939; 169 Hashmi, Tlili, Perrin, Lowndes, Peradziryi, Brickman, Martínez Arias, Lenne (2023.09.22.559003v2.16) 2022; 11 Arnold, Robertson (2023.09.22.559003v2.2) 2009; 10 Caldarelli, Chamolly, Alegria-Prevot, Gros, Corson (2023.09.22.559003v2.25) 2021 Voiculescu, Bertocchini, Wolpert, Keller, Stern (2023.09.22.559003v2.23) 2007; 449 Suppinger, Zinner, Aizarani, Lukonin, Ortiz, Azzi, Stadler, Vianello, Palla, Kohler, Mayran, Lutolf, Liberali (2023.09.22.559003v2.17) 2023 Solnica-Krezel, Sepich (2023.09.22.559003v2.1) 2012; 28 Matsuda, Yamanaka, Uemura, Osawa, Saito, Nagahashi, Nishio, Guo, Ikegawa, Sakurai (2023.09.22.559003v2.14) 2020; 580 Sutherland (2023.09.22.559003v2.56) 2016; 55 |
| References_xml | – volume: 120 start-page: e2214205120 year: 2023 ident: 2023.09.22.559003v2.21 publication-title: Proceedings of the National Academy of Sciences – volume: 4 start-page: e07090 year: 2015 ident: 2023.09.22.559003v2.18 publication-title: eLife – volume: 141 start-page: 401 year: 1963 ident: 2023.09.22.559003v2.29 publication-title: Science – start-page: 674 year: 1981 end-page: 679 ident: 2023.09.22.559003v2.28 publication-title: in Proceedings of the 7th international joint conference on Artificial intelligence - Volume 2, IJCAI’81 – volume: 18 start-page: 2672 year: 2022 ident: 2023.09.22.559003v2.48 publication-title: Soft Matter – volume: 144 start-page: 3894 year: 2017 ident: 2023.09.22.559003v2.26 publication-title: Development – volume: 28 start-page: 687 year: 2012 ident: 2023.09.22.559003v2.1 publication-title: Annual Review of Cell and Developmental Biology – volume: 128 start-page: 53 year: 1955 ident: 2023.09.22.559003v2.42 publication-title: Journal of Experimental Zoology – volume: 141 start-page: 401 year: 1963 ident: 2023.09.22.559003v2.43 publication-title: Science (New York, N.Y – volume: 429 start-page: 109943 year: 2021 ident: 2023.09.22.559003v2.36 publication-title: Journal of Computational Physics – volume: 2 start-page: 42 year: 2008 ident: 2023.09.22.559003v2.49 publication-title: HFSP J – volume: 30 start-page: 2984 year: 2020 ident: 2023.09.22.559003v2.52 publication-title: Current Biology – volume: 580 start-page: 124 year: 2020 ident: 2023.09.22.559003v2.14 publication-title: Nature – volume: 85 start-page: 031907 year: 2012 ident: 2023.09.22.559003v2.38 publication-title: Physical Review E – volume: 28 start-page: 230 year: 2021 ident: 2023.09.22.559003v2.15 publication-title: Cell stem cell – volume: 278 start-page: 255 year: 2005 ident: 2023.09.22.559003v2.30 publication-title: Developmental Biology – volume: 370 start-page: eaba4937 year: 2020 ident: 2023.09.22.559003v2.13 publication-title: Science – volume: 11 start-page: e59371 year: 2022 ident: 2023.09.22.559003v2.16 publication-title: eLife – volume: 107 start-page: 12517 year: 2010 ident: 2023.09.22.559003v2.45 publication-title: Proceedings of the National Academy of Sciences – volume: 55 start-page: 89 year: 2016 end-page: 98 ident: 2023.09.22.559003v2.56 publication-title: in Seminars in cell & developmental biology – volume: 367 start-page: 453 year: 2020 ident: 2023.09.22.559003v2.24 publication-title: Science – volume: 175 start-page: 859 year: 2018 ident: 2023.09.22.559003v2.4 publication-title: Cell – year: 2021 ident: 2023.09.22.559003v2.25 publication-title: bioRxiv – year: 2023 ident: 2023.09.22.559003v2.27 publication-title: bioRxiv doi: 10.1101/2023.01.27.525895 – volume: 101 start-page: 023309 year: 2020 ident: 2023.09.22.559003v2.35 publication-title: Physical Review E – volume: 9 start-page: 1 year: 2020 ident: 2023.09.22.559003v2.53 publication-title: eLife – volume: 115 start-page: 188302 year: 2015 ident: 2023.09.22.559003v2.34 publication-title: Physical Review Letters – volume: 18 start-page: 3771 year: 2022 ident: 2023.09.22.559003v2.39 publication-title: Soft Matter – volume: 169 year: 1939 ident: 2023.09.22.559003v2.41 publication-title: Arch Exptl Zellforsch Gewebezucht – year: 2020 ident: 2023.09.22.559003v2.8 publication-title: Nature doi: 10.1038/s41586-020-2024-3 – volume: 10 start-page: 91 year: 2009 ident: 2023.09.22.559003v2.2 publication-title: Nature reviews. Molecular cell biology – year: 2023 ident: 2023.09.22.559003v2.17 publication-title: Cell Stem Cell doi: 10.1016/j.stem.2023.04.018 – volume: 116 start-page: 25430 year: 2019 ident: 2023.09.22.559003v2.22 publication-title: Proceedings of the National Academy of Sciences – volume: 562 start-page: 272 year: 2018 ident: 2023.09.22.559003v2.7 publication-title: Nature – year: 2022 ident: 2023.09.22.559003v2.3 publication-title: bioRxiv doi: 10.1101/2022.08.01.502159 – volume: 61 start-page: 267 year: 1976 ident: 2023.09.22.559003v2.44 publication-title: Journal of theoretical biology – volume: 449 start-page: 1049 year: 2007 ident: 2023.09.22.559003v2.23 publication-title: Nature – volume: 17 start-page: 397 year: 2015 ident: 2023.09.22.559003v2.19 publication-title: Nature Cell Biology – volume: 28 year: 2016 ident: 2023.09.22.559003v2.40 publication-title: Physics of Fluids – volume: 7 start-page: L031101 year: 2022 ident: 2023.09.22.559003v2.55 publication-title: Phys. Rev. Fluids – year: 2023 ident: 2023.09.22.559003v2.47 publication-title: A combination of convergent extension and differential adhesion explains the shapes of elongating gastruloids – volume: 338 start-page: 253 year: 2012 ident: 2023.09.22.559003v2.32 publication-title: Science – volume: 64 start-page: 78 year: 2020 ident: 2023.09.22.559003v2.10 publication-title: Current Opinion in Genetics & Development Cell Reprogramming, Regeneration and Repair – volume: 582 start-page: 410 year: 2020 ident: 2023.09.22.559003v2.9 publication-title: Nature – volume: 6 start-page: 1 year: 2016 ident: 2023.09.22.559003v2.33 publication-title: Scientific Reports – volume: 31 start-page: 747 year: 2021 ident: 2023.09.22.559003v2.11 publication-title: Trends in Cell Biology – volume: 582 start-page: 405 year: 2020 ident: 2023.09.22.559003v2.12 publication-title: Nature – volume: 367 start-page: 453 year: 2020 ident: 2023.09.22.559003v2.20 publication-title: Science – volume: 141 start-page: 4231 year: 2014 ident: 2023.09.22.559003v2.6 publication-title: Development – volume: 428 year: 2002 ident: 2023.09.22.559003v2.37 publication-title: Interfacial Phenomena and the Marangoni Effect, CISM International Centre for Mechanical Sciences – volume: 8 start-page: e52554 year: 2013 ident: 2023.09.22.559003v2.50 publication-title: PloS one – volume: 338 start-page: 212 year: 2012 ident: 2023.09.22.559003v2.31 publication-title: Science – volume: 25 start-page: 013022 year: 2023 ident: 2023.09.22.559003v2.51 publication-title: New Journal of Physics – volume: 8 start-page: e42434 year: 2019 ident: 2023.09.22.559003v2.5 publication-title: eLife – volume: 24 start-page: 1341 year: 2022 ident: 2023.09.22.559003v2.46 publication-title: Nature Cell Biology – volume: 561 start-page: 401 year: 2018 ident: 2023.09.22.559003v2.54 publication-title: Nature |
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| Title | Marangoni-like tissue flows enhance symmetry breaking of embryonic organoids |
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