Regulation of tissue morphodynamics: an important role for actomyosin contractility

Siedlik, Michael J.; Nelson, Celeste M.

doi:10.1016/j.gde.2015.01.002

Cited by 27 publications

(22 citation statements)

References 51 publications

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“…4D) [48]. A contractile network of actomyosin, which spans the apical surface of these cells, constricts to reduce the apical surface area and generate wedge-shaped epithelial cells [49, 50]. A continuum mechanical model of the developing airway epithelium (Fig.…”

Section: Physical Modelsmentioning

confidence: 99%

Computational models of airway branching morphogenesis

Varner¹,

Nelson²

2017

Seminars in Cell & Developmental Biology

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The bronchial network of the mammalian lung consists of millions of dichotomous branches arranged in a highly complex, space-filling tree. Recent computational models of branching morphogenesis in the lung have helped uncover the biological mechanisms that construct this ramified architecture. In this review, we focus on three different theoretical approaches – geometrical modeling, reaction-diffusion modeling, and continuum mechanical modeling – and discuss how, taken together, these models have identified the geometrical principles necessary to build an efficient bronchial network, as well as the patterning mechanisms that specify the airway geometry in the developing embryo. We emphasize models that are integrated with biological experiments and suggest how recent progress in computational modeling has advanced our understanding of airway branching morphogenesis.

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Section: Physical Modelsmentioning

confidence: 99%

Computational models of airway branching morphogenesis

Varner¹,

Nelson²

2017

Seminars in Cell & Developmental Biology

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“…Epithelial cell sheets dynamically restructure their shapes to sculpt higher order assemblies of tissues and organs (1)(2)(3). Constituent cells execute complex shape changes that require coordinated mechanisms to alter cell-cell junction lengths, cell surface area, and overall cell shape (4).…”

Section: Introductionmentioning

confidence: 99%

RhoA mediates epithelial cell shape changes via mechanosensitive endocytosis

Cavanaugh

Staddon

Munro

et al. 2019

Preprint

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Morphogenetic movements require tight spatiotemporal control over cell-cell junction lengths. Contractile forces, acting at adherens junctions, alter cell-cell contact lengths in a cyclic fashion as a mechanical ratchet. Pulsatile RhoA activity is thought to drive ratcheting through acute periods of junction contraction followed by stabilization. Currently, we lack a mechanistic understanding of if and how RhoA activity governs junction length and subsequent cell shape within epithelia. In this study we use optogenetics to exogenously control RhoA activity in model Caco-2 epithelium. We find that at short timescales, RhoA activation drives reversible junction contraction. Sustained RhoA activity drives irreversible junction shortening but the amount of shortening saturates for a single pulse. To capture these data, we develop a vertex model modified to include straindependent junction length and tension remodeling. We find that, to account for experimental data, tension remodeling requires a strain-dependent threshold. Our model predicts that temporal structuring of RhoA activity allows for subsequent tension remodeling events to overcome the limited shortening within a single pulse and this is confirmed by our experimental data. We find that RhoAmediated junction remodeling requires activities of formin and dynamin, indicating the closely interconnected activities of contractility, E-cadherin clustering, and endocytosis. Junction length is therefore regulated by the coordinated action of RhoA-mediated contractility, membrane trafficking, and adhesion receptor remodeling. Altogether these data provide insights into the underlying molecular and biophysical mechanisms of RhoA-mediated regulation of epithelial cell shape.

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“…Given their role in cell migration, it is apparent that traction forces are also likely to be important in various morphogenetic processes [86–89]. Indeed, the role of mechanical forces in embryonic development has been recognized since the early 20 th century [90].…”

Section: Application 2: Forces Exerted During Tissue Morphogenesismentioning

confidence: 99%

“…Several excellent reviews discuss morphogenesis in a broader context [88,89,100], as well as the role of mechanical forces in morphogenesis [101,102,13,103,87]. Quantifying traction forces in vivo remains a key challenge that must be addressed in order to fully understand the role of these forces in morphogenesis.…”

Section: Application 2: Forces Exerted During Tissue Morphogenesismentioning

confidence: 99%

Microfabricated tissues for investigating traction forces involved in cell migration and tissue morphogenesis

Nerger

Siedlik

Nelson

2016

Cell. Mol. Life Sci.

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Cell-generated forces drive an array of biological processes ranging from wound healing to tumor metastasis. Whereas experimental techniques such as traction force microscopy are capable of quantifying traction forces in multidimensional systems, the physical mechanisms by which these forces induce changes in tissue form remain to be elucidated. Understanding these mechanisms will ultimately require techniques that are capable of quantifying traction forces with high precision and accuracy in vivo or in systems that recapitulate in vivo conditions, such as microfabricated tissues and engineered substrata. To that end, here we review the fundamentals of traction forces, their quantification, and the use of microfabricated tissues designed to study these forces during cell migration and tissue morphogenesis. We emphasize the differences between traction forces in two- and three-dimensional systems, and highlight recently developed techniques for quantifying traction forces.

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Regulation of tissue morphodynamics: an important role for actomyosin contractility

Cited by 27 publications

References 51 publications

Computational models of airway branching morphogenesis

Computational models of airway branching morphogenesis

RhoA mediates epithelial cell shape changes via mechanosensitive endocytosis

Microfabricated tissues for investigating traction forces involved in cell migration and tissue morphogenesis

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