When the Community Silences Disruptive Elements: Multiscale Mechanical Coupling Buffers Morphogenetic Imprecisions

Martin, Emmanuel

doi:10.1016/j.devcel.2020.03.024

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…The precise mechanisms leading to enhanced patterning upon actuation remain to be elucidated. It is possible that actuation confers developmental robustness and that fluctuations in contractility or PCP gene expression may be buffered by tissue-scale mechanical coupling, as has recently been shown during drosophila gastrulation 49,50 . The engineered platform we describe here to mechanically actuate 3D organoids, and the accompanying single-cell atlas, can be used in conjunction with synthetic matrices to completely specify the extrinsic mechanical state of organoids.…”

Section: Resultsmentioning

confidence: 99%

Actuation enhances patterning in human neural tube organoids

et al. 2021

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Tissues achieve their complex spatial organization through an interplay between gene regulatory networks, cell-cell communication, and physical interactions mediated by mechanical forces. Current strategies to generate in-vitro tissues have largely failed to implement such active, dynamically coordinated mechanical manipulations, relying instead on extracellular matrices which respond to, rather than impose mechanical forces. Here, we develop devices that enable the actuation of organoids. We show that active mechanical forces increase growth and lead to enhanced patterning in an organoid model of the neural tube derived from single human pluripotent stem cells (hPSC). Using a combination of single-cell transcriptomics and immunohistochemistry, we demonstrate that organoid mechanoregulation due to actuation operates in a temporally restricted competence window, and that organoid response to stretch is mediated extracellularly by matrix stiffness and intracellularly by cytoskeleton contractility and planar cell polarity. Exerting active mechanical forces on organoids using the approaches developed here is widely applicable and should enable the generation of more reproducible, programmable organoid shape, identity and patterns, opening avenues for the use of these tools in regenerative medicine and disease modelling applications.

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Section: Resultsmentioning

confidence: 99%

Actuation enhances patterning in human neural tube organoids

et al. 2021

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“…However it ignores the mechanical source of the growth, which, as argued in this thesis, is so important for understanding developmental patterning. Indeed, as discussed above in the section on embodiment, mechanics likely plays a critical role in generating the coordination of growth between neighboring cell files, through smoothing over local differences (Martin and Suzanne, 2020).…”

Section: Inclusion Of Mechanicsmentioning

confidence: 99%

Growing up and down the root

Rutten¹

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Computational models are invaluable tools for understanding the hormonal and genetic control of root development. Thus far, models have focused on the crucial roles that auxin transport and metabolism play in determining the auxin signaling gradient that controls the root meristem. Other hormones such as cytokinins, gibberellins, and ethylene have predominantly been considered as modulators of auxin dynamics, but their underlying patterning mechanisms are currently unresolved. In addition, the effects of cell-and tissuelevel growth dynamics, which induce dilution and displacement of signaling molecules, have remained unexplored. Elucidating these additional mechanisms will be essential to unravel how root growth is patterned in a robust and self-organized manner. Models incorporating growth will thus be crucial in unraveling the underlying logic of root developmental decision making. HighlightsComputational models are an important tool in unraveling the complex patterning processes underlying root growth and development. They enable integrating processes playing out at different spatial and temporal scales, and allow for systematic variation of their components, enabling us to identify the core mechanisms driving patterning.

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Actuation Enhances Patterning in Human Neural Tube Organoids

Fattah

Daza

Rustandi

et al. 2020

Preprint

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Tissues achieve their complex spatial organization through an interplay between gene regulatory networks, cell-cell communication, and physical interactions mediated by mechanical forces. Current strategies to generate in-vitro tissues have largely failed to implement such active, dynamically coordinated mechanical manipulations, relying instead on extracellular matrices which respond to, rather than impose mechanical forces. Here we develop devices that enable the actuation of organoids. We show that active mechanical forces increase growth and lead to enhanced patterning in an organoid model of the neural tube derived from single human pluripotent stem cells (hPSC). Using a combination of single-cell transcriptomics and immunohistochemistry, we demonstrate that organoid mechanoregulation due to actuation operates in a temporally restricted competence window, and that organoid response to stretch is mediated extracellularly by matrix stiffness and intracellularly by cytoskeleton contractility and planar cell polarity. Exerting active mechanical forces on organoids using the approaches developed here is widely applicable and should enable the generation of more reproducible, programmable organoid shape, identity and patterns, opening avenues for the use of these tools in regenerative medicine and disease modelling applications.

show abstract

When the Community Silences Disruptive Elements: Multiscale Mechanical Coupling Buffers Morphogenetic Imprecisions

Cited by 3 publications

References 9 publications

Actuation enhances patterning in human neural tube organoids

Actuation enhances patterning in human neural tube organoids

Growing up and down the root

Actuation Enhances Patterning in Human Neural Tube Organoids

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