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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Cold Spring Harbor Laboratory
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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| License | This pre-print is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), CC BY-NC 4.0, as described at http://creativecommons.org/licenses/by-nc/4.0 |
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| Notes | Competing Interest Statement: The authors have declared no competing interest. |
| ORCID | 0000-0003-4195-7792 0000-0001-6018-9923 0000-0003-1066-7506 0000-0001-9118-1270 |
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| Title | Marangoni-like tissue flows enhance symmetry breaking of embryonic organoids |
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