A Mechanosensitive RhoA Pathway that Protects Epithelia against Acute Tensile Stress

Acharya, Bipul R.; Nestor-Bergmann, Alexander; Liang, Xuan; Gupta, Shafali; Duszyc, Kinga; Gauquelin, Estelle; Gómez, Guillermo A.; Budnar, Srikanth; Marcq, Philippe; Jensen, Oliver E.; Bryant, Zev; Yap, Alpha S.

doi:10.1016/j.devcel.2018.09.016

Cited by 130 publications

(105 citation statements)

References 76 publications

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“…This result, together with the fact that MyoVI is involved in Rho-dependent activation of 420 actin-myosin cytoskeleton (Acharya et al, 2018), suggests that MyoVI is a molecular 421 component of the mechanosensitive feedback we describe in our self-organized model. 422…”

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confidence: 67%

“…In order to test our prediction that the reduction of mechanosensitivity will reduce the 352 magnitude of cell elongation, we used RNAi to knockdown Myosin VI, a molecular motor 353 implicated in mechanosignaling. Myosin VI is an upstream component of a Rho-dependent 354 signaling pathway that reorganizes the actin-myosin cytoskeleton in response to mechanical 355 stress (Acharya et al, 2018). Experiments in wing discs also indicate that mechanosensation 356…”

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confidence: 99%

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Self-organized patterning of cell morphology via mechanosensitive feedback

Dye

Popović

Iyer

et al. 2020

Preprint

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16Tissue organization is often characterized by specific patterns of cell morphology. How 17 such patterns emerge in developing tissues is a fundamental open question. Here, we 18 investigate the emergence of tissue-scale patterns of cell shape and mechanical tissue 19 stress in the Drosophila wing imaginal disc during larval development. Using quantitative 20analysis of the cellular dynamics, we reveal a pattern of radially oriented cell rearrangements 21that is coupled to the buildup of tangential cell elongation. Developing a laser ablation 22 method, we map tissue stresses and extract key parameters of tissue mechanics. We 23 present a continuum theory showing that this pattern of cell morphology and tissue stress 24can arise via self-organization of a mechanical feedback that couples cell polarity to active 25 cell rearrangements. The predictions of this model are supported by knockdown of MyoVI, a 26 component of mechanosensitive feedback. Our work reveals a mechanism for the 27 emergence of cellular patterns in morphogenesis. 28

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confidence: 67%

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confidence: 99%

Self-organized patterning of cell morphology via mechanosensitive feedback

Dye

Popović

Iyer

et al. 2020

Preprint

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“…Even without myosin contractility, cross‐linked networks of actin can exhibit a range of stiffnesses and mechanical properties (Bieling et al, ). In the wing disk, normal stress leads to the reinforcement of AJs (Kale et al, ; Pinheiro & Bellaïche, ; Venkatesan Iyer, Piscitello‐Gómez, Paijmans, Jülicher, & Eaton, ) and the reorientation of actomyosin to resist deformation (Acharya et al, ; Duda et al, ). Modulation of mechanical properties can thereby influence the stress and strain distributions and may thereby affect growth in the disk.…”

Section: The Role Of Mechanical Forces In Wing Disk Morphogenesismentioning

confidence: 99%

Growth control in the Drosophila wing disk

Gou

Stotsky

Othmer

2020

WIREs Mechanisms of Disease

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The regulation of size and shape is a fundamental requirement of biological development and has been a subject of scientific study for centuries, but we still lack an understanding of how organisms know when to stop growing. Imaginal wing disks of the fruit fly Drosophila melanogaster, which are precursors of the adult wings, are an archetypal tissue for studying growth control. The growth of the disks is dependent on many inter‐ and intra‐organ factors such as morphogens, mechanical forces, nutrient levels, and hormones that influence gene expression and cell growth. Extracellular signals are transduced into gene‐control signals via complex signal transduction networks, and since cells typically receive many different signals, a mechanism for integrating the signals is needed. Our understanding of the effect of morphogens on tissue‐level growth regulation via individual pathways has increased significantly in the last half century, but our understanding of how multiple biochemical and mechanical signals are integrated to determine whether or not a cell decides to divide is still rudimentary. Numerous fundamental questions are involved in understanding the decision‐making process, and here we review the major biochemical and mechanical pathways involved in disk development with a view toward providing a basis for beginning to understand how multiple signals can be integrated at the cell level, and how this translates into growth control at the level of the imaginal disk. This article is categorized under: Analytical and Computational Methods > Computational Methods Biological Mechanisms > Cell Signaling Models of Systems Properties and Processes > Cellular Models

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“…Cyst is the single orthologue of a group of four mammalian RhoGEFs that target RhoA in cell culture (Cook et al, 2014). One of the mammalian orthologs, p114RhoGEF stabilizes tight junctions and AJs through the organization of actin cytoskeleton associated with cellular junctions (Nakajima and Tanoue, 2010;Terry et al, 2011;Acharya et al, 2018).…”

Section: Cyst and Its Mammalian Orthologs Share A Conserved Functionmentioning

confidence: 99%

The RhoGEF Cysts couples apical polarity proteins to Rho and myosin activity at adherens junctions

Silver

Wirtz-Peitz²,

Simões

et al. 2019

Preprint

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The spatio-temporal regulation of small Rho GTPases is crucial for the dynamic stability of epithelial tissues. However, how RhoGTPase activity is controlled during development remains largely unknown. To explore the regulation of Rho GTPases in vivo we analyzed the Rho GTPase guanine nucleotide exchange factor (RhoGEF) Cysts, the Drosophila orthologue of mammalian p114RhoGEF, GEF-H1, p190RhoGEF, and AKAP-13. Loss of Cysts causes a phenotype that closely resemble the mutant phenotype of the apical polarity regulator Crumbs.This phenotype can be suppressed by the loss of basolateral polarity proteins suggesting that Cysts in an integral component of the apical polarity protein network. Cysts activates Rho at adherens junctions to promote junctional enrichment of myosin II, which requires the RhoGEF domain and the coiled-coil domain containing C-terminal region of Cysts. Cysts recruitment to the apico-lateral cortex depends on Crumbs and Bazooka/Par3 and requires multiple domains within Cysts including the C-terminal region. Together, our findings indicate that Cysts links apical polarity proteins to Rho1 and myosin activation at adherens junctions to support junctional and epithelial integrity in the Drosophila ectoderm.

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A Mechanosensitive RhoA Pathway that Protects Epithelia against Acute Tensile Stress

Cited by 130 publications

References 76 publications

Self-organized patterning of cell morphology via mechanosensitive feedback

Self-organized patterning of cell morphology via mechanosensitive feedback

Growth control in the Drosophila wing disk

The RhoGEF Cysts couples apical polarity proteins to Rho and myosin activity at adherens junctions

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