Actomyosin stiffens the vertebrate embryo during crucial stages of elongation and neural tube closure

Zhou, Jian; Kim, Hye Young; Davidson, Lance A.

doi:10.1242/dev.026211

Cited by 202 publications

(277 citation statements)

References 63 publications

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“…23 In developing Xenopus embryos, a temporal and spatial distribution of mechanical stiffness directs early patterning and differentiation events, with cells creating these gradients of stiffness through actomyosin contraction. 24 Zhou and coworkers found that profound tissue stiffening occurs from the gastrula to neurula stages, and this stiffening had an impact on neural tube formation. By treating tissue explants with latrunculin B, an actin-depolymerizing drug used to reduce actomyosin contraction, the researchers were able to reduce tissue stiffness by more than 50%, suggesting that cell-mediated actomyosin contractility is responsible for much of the tissue stiffening that occurs during this stage of development.…”

Section: Cellular Response To Ecm Stiffness During Embryonic Developmentmentioning

confidence: 99%

“…25 Similarly, patterning of the anteroposterior axis is stabilized by the generation of actomyosin-based tension, which acts to organize and stiffen the ECM in the paraxial somatic mesoderm. 24 Tight junctions and adherens junctions mediate the forces exerted between cells to compartmentalize these developing tissues. Additionally, myosin II is enriched at sites of tension application on the surface of intercalating cells, 26 suggesting that anisotropy in the micromechanical environment contributes significantly to pattern formation.…”

Section: Cellular Response To Ecm Stiffness During Embryonic Developmentmentioning

confidence: 99%

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Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression

et al. 2015

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ABSTRACT. Tissue development is orchestrated by the coordinated activities of both chemical and physical regulators. While much attention has been given to the role that chemical regulators play in driving development, researchers have recently begun to elucidate the important role that the mechanical properties of the extracellular environment play. For instance, the stiffness of the extracellular environment has a role in orienting cell division, maintaining tissue boundaries, directing cell migration, and driving differentiation. In addition, extracellular matrix stiffness is important for maintaining normal tissue homeostasis, and when matrix mechanics become imbalanced, disease progression may ensue. In this article, we will review the important role that matrix stiffness plays in dictating cell behavior during development, tissue homeostasis, and disease progression.

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Section: Cellular Response To Ecm Stiffness During Embryonic Developmentmentioning

confidence: 99%

Section: Cellular Response To Ecm Stiffness During Embryonic Developmentmentioning

confidence: 99%

Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression

et al. 2015

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“…Our model produces strain patterns similar to those observed in experiments. Based on previous measurements of the viscoelastic material properties of Xenopus embryos (18,19), the shear modulus ranges from 3 to 15 Pa over these stages. Our FE model shows how tissues displace beyond the area exposed to ATP.…”

Section: Significancementioning

confidence: 99%

“…S13). Such a wave velocity is sustained in Xenopus embryonic tissues rather than being immediately damped because the time constant of viscoelastic dissipation, ∼60 s, is longer than the time taken by a wave to pass through the tissue (18,19). The kinematics of these wave-like contraction responses to periodic stimulations can be understood and predictably simulated using system dynamics theory.…”

Section: Significancementioning

confidence: 99%

Mechanochemical actuators of embryonic epithelial contractility

Kim

Hazar

Vijayraghavan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

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Spatiotemporal regulation of cell contractility coordinates cell shape change to construct tissue architecture and ultimately directs the morphology and function of the organism. Here we show that contractility responses to spatially and temporally controlled chemical stimuli depend much more strongly on intercellular mechanical connections than on biochemical cues in both stimulated tissues and adjacent cells. We investigate how the cell contractility is triggered within an embryonic epithelial sheet by local ligand stimulation and coordinates a long-range contraction response. Our custom microfluidic control system allows spatiotemporally controlled stimulation with extracellular ATP, which results in locally distinct contractility followed by mechanical strain pattern formation. The stimulationresponse circuit exposed here provides a better understanding of how morphogenetic processes integrate responses to stimulation and how intercellular responses are transmitted across multiple cells. These findings may enable one to create a biological actuator that actively drives morphogenesis.microfluidics | multicellular | mechanotransduction | signaling P hysiological control systems have evolved diverse strategies to sense the environment, transduce signals, and actuate contractile responses. One such strategy involves the actuation of nonmuscle cell contractility to drive a wide range of developmental processes as well as normal physiological and pathological disease states (1-5). The contractile behaviors of cells and their interactions in multicellular arrays are not only critical in shaping and guiding tissue formation (e.g., epithelial folding) for the successful outcome of development programs (6, 7), but also play a major role in the pathology of tumor growth, the invasionmetastasis cascade, wound healing, and tissue regeneration (8,9).From a signaling standpoint, embryonic development is a dynamic process where cells interact and coordinate force generation as their identities are patterned by spatiotemporally applied chemical stimuli. There has been considerable debate over the effectiveness of intra-versus intercellular signaling during development (10, 11); nevertheless, the cell-cell signaling and the coordination of a variety of multicellular responses are known to be mediated by gap-junction-dependent intercellular communication (12, 13). However, recent findings from studies of cell mechanics indicate that mechanical cues can be as potent as chemical factors in directing cell differentiation and behaviors and suggest a role in modulating signal transduction pathways (14, 15). Less clear is whether signal transduction can be modulated by mechanical connections during morphogenesis. Results and DiscussionTo investigate the complex integrated response of a multicellular system and investigate the mechanochemical response and actuation, we cultured an intact epithelial sheet adhered to a fibronectin extracellular matrix substrate within a custom microfluidic chamber and exposed a narrow band of 4-5 cells...

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“…In fact, during Xenopus gastrulation, polarized morphogenetic movements are driven in a similar manner by cortical actomyosin remodeling. 48,49 Interestingly, the cytoskeletal forces from within the cells also influence signaling pathways that mediate localized assembly of extracellular matrix. 50 These results, taken together, suggest that it is possible that both the cellular and extracellular (matrix) forces/properties driving local morphogenetic movements are recruited by a common upstream signal.…”

Section: Molecular Drivers Of Local Morphogenetic Movementsmentioning

confidence: 99%

Identification of emergent motion compartments in the amniote embryo

Loganathan¹,

Little²,

Joshi³

et al. 2014

Organogenesis

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The tissue scale deformations (1mm) required to form an amniote embryo are poorly understood. Here, we studied »400 mm-sized explant units from gastrulating quail embryos. The explants deformed in a reproducible manner when grown using a novel vitelline membrane-based culture method. Time-lapse recordings of latent embryonic motion patterns were analyzed after disk-shaped tissue explants were excised from three specific regions near the primitive streak: 1) anterolateral epiblast, 2) posterolateral epiblast, and 3) the avian organizer (Hensen's node). The explants were cultured for 8 hours-an interval equivalent to gastrulation. Both the anterolateral and the posterolateral epiblastic explants engaged in concentric radial/centrifugal tissue expansion. In sharp contrast, Hensen's node explants displayed Cartesian-like, elongated, bipolar deformations-a pattern reminiscent of axis elongation. Time-lapse analysis of explant tissue motion patterns indicated that both cellular motility and extracellular matrix fiber (tissue) remodeling take place during the observed morphogenetic deformations. As expected, treatment of tissue explants with a selective Rho-Kinase (p160ROCK) signaling inhibitor, Y27632, completely arrested all morphogenetic movements. Microsurgical experiments revealed that lateral epiblastic tissue was dispensable for the generation of an elongated midline axisprovided that an intact organizer (node) is present. Our computational analyses suggest the possibility of delineating tissue-scale morphogenetic movements at anatomically discrete locations in the embryo. Further, tissue deformation patterns, as well as the mechanical state of the tissue, require normal actomyosin function. We conclude that amniote embryos contain tissue-scale, regionalized morphogenetic motion generators, which can be assessed using our novel computational time-lapse imaging approach. These data and future studies-using explants excised from overlapping anatomical positions-will contribute to understanding the emergent tissue flow that shapes the amniote embryo.

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Actomyosin stiffens the vertebrate embryo during crucial stages of elongation and neural tube closure

Cited by 202 publications

References 63 publications

Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression

Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression

Mechanochemical actuators of embryonic epithelial contractility

Identification of emergent motion compartments in the amniote embryo

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