Pulsed contractions of an actin-myosin network drive apical constriction. Nature

Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Nature (Impact Factor: 41.46). 12/2008; 457(7228):495-9. DOI: 10.1038/nature07522
Source: PubMed


Apical constriction facilitates epithelial sheet bending and invagination during morphogenesis. Apical constriction is conventionally thought to be driven by the continuous purse-string-like contraction of a circumferential actin and non-muscle myosin-II (myosin) belt underlying adherens junctions. However, it is unclear whether other force-generating mechanisms can drive this process. Here we show, with the use of real-time imaging and quantitative image analysis of Drosophila gastrulation, that the apical constriction of ventral furrow cells is pulsed. Repeated constrictions, which are asynchronous between neighbouring cells, are interrupted by pauses in which the constricted state of the cell apex is maintained. In contrast to the purse-string model, constriction pulses are powered by actin-myosin network contractions that occur at the medial apical cortex and pull discrete adherens junction sites inwards. The transcription factors Twist and Snail differentially regulate pulsed constriction. Expression of snail initiates actin-myosin network contractions, whereas expression of twist stabilizes the constricted state of the cell apex. Our results suggest a new model for apical constriction in which a cortical actin-myosin cytoskeleton functions as a developmentally controlled subcellular ratchet to reduce apical area incrementally.

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Available from: Eric Wieschaus, Sep 25, 2014
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    • "This prediction was tested using time-lapse microscopy data on the early stage of Ventral Furrow formation in the Drosophila embryo [39] [40]. The initial time point of each movie was fit to the closest possible tension net, using the variational approach defined by Eqs. "
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    ABSTRACT: It is now widely recognized that mechanical interactions between cells play a crucial role in epithelial morphogenesis, yet understanding the mechanisms through which stress and deformation affect cell behavior remains an open problem due to the complexity inherent in the mechanical behavior of cells and the difficulty of direct measurement of forces within tissues. Theoretical models can help by focusing experimental studies and by providing the framework for interpreting measurements. To that end, "vertex models" have introduced an approximation of epithelial cell mechanics based on a polygonal tiling representation of planar tissue. Here we formulate and analyze an Active Tension Network (ATN) model, which is based on the same polygonal representation of epithelial tissue geometry, but in addition i) assumes that mechanical balance is dominated by cortical tension and ii) introduces tension dependent local remodeling of the cortex, representing the active nature of cytoskeletal mechanics. The tension-dominance assumption has immediate implications for the geometry of cells, which we demonstrate to hold in certain types of Drosophila epithelial tissues. We demonstrate that stationary configurations of an ATN form a manifold with one degree of freedom per cell, corresponding to "isogonal" - i.e. angle preserving - deformations of cells, which dominate the dynamic response to perturbations. We show that isogonal modes account for approximately 90% of experimentally observed deformation of cells during the process of ventral furrow formation in Drosophila. Other interesting properties of our model include the exponential screening of mechanical stress and a negative Poisson ratio response to external uniaxial stress. We also provide a new approach to the problem of inferring local cortical tensions from the observed geometry of epithelial cells in a tissue
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    • "under the nanos germ cell promoter (Sano et al., 2005), LimK 2 (Huey Hing; Ang et al., 2006) sqh P -sqh::mCherry A11 (Adam Martin; Martin et al., 2009), aurB 1689 and UAS-SvnS12 5E (Jean-René Huynh; Mathieu et al., 2013), and UAS-egfr DN (Trudi Schupbach). All remaining stocks—UAS-ssh ( "
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    ABSTRACT: In many tissues, the stem cell niche must coordinate behavior across multiple stem cell lineages. How this is achieved is largely unknown. We have identified delayed completion of cytokinesis in germline stem cells (GSCs) as a mechanism that regulates the production of stem cell daughters in the Drosophila testis. Through live imaging, we show that a secondary F-actin ring is formed through regulation of Cofilin activity to block cytokinesis progress after contractile ring disassembly. The duration of this block is controlled by Aurora B kinase. Additionally, we have identified a requirement for somatic cell encystment of the germline in promoting GSC abscission. We suggest that this non-autonomous role promotes coordination between stem cell lineages. These findings reveal the mechanisms by which cytokinesis is inhibited and reinitiated in GSCs and why such complex regulation exists within the stem cell niche. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Jul 2015 · Developmental Cell
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    • "The pathway leading to these phosphorylation events in Drosophila gastrulation are triggered by a well-understood cascade of events that commences with the mesodermal-specific expression of G protein-coupled receptors that apically recruit a guanine exchange factor (DRhoGEF2). DRhoGEF2 activates the Rho-GTPase, Rho1 and in turn stimulates phosphorylation by activating the serine–threonine kinase Rok (Sawyer et al., 2010). Once active, contraction occurs in a step-wise manner consisting of pulses interspersed by periods of relaxation or apical surface stabilization (Azevedo et al., 2011; Blanchard, Murugesu, Adams, Martinez-Arias, & Gorfinkiel, 2010; David, Tishkina, & Harris, 2010; Martin et al., 2009). A molecular connection bridging actomyosin to junctional complexes are also necessary to draw the apical circumference inward and when disrupted the degree of AC is attenuated (Dawes-Hoang et al., 2005; Roh-Johnson et al., 2012; Sawyer, Harris, Slep, Gaul, & Peifer, 2009). "
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    ABSTRACT: Morphogenesis is the developmental process by which tissues and organs acquire the shape that is critical to their function. Here, we review recent advances in our understanding of the mechanisms that drive morphogenesis in the developing eye. These investigations have shown that regulation of the actin cytoskeleton is central to shaping the presumptive lens and retinal epithelia that are the major components of the eye. Regulation of the actin cytoskeleton is mediated by Rho family GTPases, by signaling pathways and indirectly, by transcription factors that govern the expression of critical genes. Changes in the actin cytoskeleton can shape cells through the generation of filopodia (that, in the eye, connect adjacent epithelia) or through apical constriction, a process that produces a wedge-shaped cell. We have also learned that one tissue can influence the shape of an adjacent one, probably by direct force transmission, in a process we term inductive morphogenesis. Though these mechanisms of morphogenesis have been identified using the eye as a model system, they are likely to apply broadly where epithelia influence the shape of organs during development. © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Feb 2015 · Current Topics in Developmental Biology
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