Integration of luminal pressure and signalling in tissue self-organization

Chan, Chii Jou; Hiiragi, Takashi

doi:10.1242/dev.181297

Cited by 49 publications

(46 citation statements)

References 102 publications

(135 reference statements)

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“…For example, smooth muscle cells are not necessary for the initiation of cleft formation (Figure 2D) 50 , but should mechanically assist the cleft formation from the outside of an epithelium, realizing the stable terminal bifurcation 27,50 . Luminal fluid is another potentially important factor that can mechanically affect epithelial tissue deformation through shear stress and hydrostatic pressure 51 . It has been previously reported that the manipulation of luminal pressure in murine developing lungs under ex vivo culture conditions altered branch formation 34 .…”

Section: Discussionmentioning

confidence: 99%

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ERK-mediated Curvature Feedback Regulates Branching Morphogenesis in Lung Epithelial Tissue

Hirashima

2021

Preprint

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Intricate branching patterns emerge in internal organs because of the repetitive presence of simple deformations in epithelial tissues. During murine lung development, epithelial cells in distal tips of a single tube require fibroblast growth factor (FGF) signals generated by their surrounding mesenchyme to form repetitive tip bifurcations. However, it remains unknown how the cells employ FGF signaling to convert their behaviors to achieve the recursive branching processes. Here we show a self-sustained epithelial regulatory system during the murine lung branching morphogenesis, mediated by extracellular signal-regulated kinase (ERK), which acts as a downstream driver of FGF signaling. We found that tissue-scale curvature regulates ERK activity in the lung epithelium using two-photon live cell imaging and mechanical perturbations. ERK is activated specifically in epithelial tissues with a positive curvature, regardless of whether the change in curvature was attributable to morphogenesis or artificial perturbations. Moreover, we found that ERK activation accelerates actin polymerization specifically at the apical side of cells, and mechanically contributes to the extension of the apical membrane, leading to a decrease in epithelial tissue curvature. These results indicate the existence of a negative feedback loop between tissue curvature and ERK activity beyond scale. We confirmed that this regulation was sufficient to generate the recursive branching processes by a mathematical model. Taken together, we propose that ERK mediates the curvature feedback loop underlying the process of branching morphogenesis in developing lungs.

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Section: Discussionmentioning

confidence: 99%

“…The second term of Equation 5 represents the mechanical effect of luminal pressure 34,35,51 on the apical edge of epithelial cells. The function f was defined as…”

Section: (Iic) Mathematical Modeling For Multicellular Dynamicsmentioning

confidence: 99%

ERK-mediated Curvature Feedback Regulates Branching Morphogenesis in Lung Epithelial Tissue

Hirashima

2021

Preprint

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“…In turn, luminal pressure leads to increased cortical tension in the TE and tight junction maturation to allow lumen expansion ( Chan et al, 2019 ). This is a perfect example of how mechanical cues, in this case hydrostatic pressure, affect differentiation ( Chan and Hiiragi, 2020 ).…”

Section: The Implanting Embryo: a Global Transformationmentioning

confidence: 99%

Mechanisms of human embryo development: from cell fate to tissue shape and back

2020

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Gene regulatory networks and tissue morphogenetic events drive the emergence of shape and function: the pillars of embryo development. Although model systems offer a window into the molecular biology of cell fate and tissue shape, mechanistic studies of our own development have so far been technically and ethically challenging. However, recent technical developments provide the tools to describe, manipulate and mimic human embryos in a dish, thus opening a new avenue to exploring human development. Here, I discuss the evidence that supports a role for the crosstalk between cell fate and tissue shape during early human embryogenesis. This is a critical developmental period, when the body plan is laid out and many pregnancies fail. Dissecting the basic mechanisms that coordinate cell fate and tissue shape will generate an integrated understanding of early embryogenesis and new strategies for therapeutic intervention in early pregnancy loss.

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“…The mechanism of luminogenesis has been extensively investigated with 3D-cultured MDCK cells (MDCK: Madin-Derby Canine Kidney cell line) [ 39 ]. The mechanical cues mediated by lumen enlargement and oscillations are also essential during embryo development [ 40 ]. Strikingly, the release of the blastocyst from the zona pellucida is driven by an active swelling and shrinking of the lumen.…”

Section: Discussionmentioning

confidence: 99%

Long-term live imaging and multiscale analysis identify heterogeneity and core principles of epithelial organoid morphogenesis

et al. 2021

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Background Organoids are morphologically heterogeneous three-dimensional cell culture systems and serve as an ideal model for understanding the principles of collective cell behaviour in mammalian organs during development, homeostasis, regeneration, and pathogenesis. To investigate the underlying cell organisation principles of organoids, we imaged hundreds of pancreas and cholangiocarcinoma organoids in parallel using light sheet and bright-field microscopy for up to 7 days. Results We quantified organoid behaviour at single-cell (microscale), individual-organoid (mesoscale), and entire-culture (macroscale) levels. At single-cell resolution, we monitored formation, monolayer polarisation, and degeneration and identified diverse behaviours, including lumen expansion and decline (size oscillation), migration, rotation, and multi-organoid fusion. Detailed individual organoid quantifications lead to a mechanical 3D agent-based model. A derived scaling law and simulations support the hypotheses that size oscillations depend on organoid properties and cell division dynamics, which is confirmed by bright-field microscopy analysis of entire cultures. Conclusion Our multiscale analysis provides a systematic picture of the diversity of cell organisation in organoids by identifying and quantifying the core regulatory principles of organoid morphogenesis.

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Integration of luminal pressure and signalling in tissue self-organization

Cited by 49 publications

References 102 publications

ERK-mediated Curvature Feedback Regulates Branching Morphogenesis in Lung Epithelial Tissue

ERK-mediated Curvature Feedback Regulates Branching Morphogenesis in Lung Epithelial Tissue

Mechanisms of human embryo development: from cell fate to tissue shape and back

Long-term live imaging and multiscale analysis identify heterogeneity and core principles of epithelial organoid morphogenesis

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