A global pattern of mechanical stress polarizes cell divisions and cell shape in the growing Drosophila wing disc

Organismal development is under genetic control. Ultimately, mechanical forces shape embryos. If we want to understand the precise regulation of size and shape in animals, we must dissect how forces are distributed in developing tissues, and how they drive cell behavior to shape organs. This has not been addressed fully in the context of growing tissues. As cells grow and divide, they exert a pressure on their neighbors. How these local stresses add up or dissipate as the tissue grows is an unanswered question. We address this issue in the growing wing imaginal disc of Drosophila larvae, the precursor of the adult wing. We used a quantitative approach to analyze the strains and stresses of cells of the wing pouch, and found a global pattern of stress whereby cells in the periphery of the tissue are mechanically stretched and cells in the center are compressed. This pattern has important consequences on cell shape in the wing pouch: cells respond to it by polarizing their acto-myosin cortex, and aligning their divisions with the main axis of cell stretch, thereby polarizing tissue growth. Ectopic perturbations of tissue growth by the Hippo signaling pathway reorganize this pattern in a non-autonomous manner, suggesting a synergy between tissue mechanics and growth control during wing disc morphogenesis.

[1]  Françoise Brochard-Wyart,et al.  Mechanosensitive shivering of model tissues under controlled aspiration , 2011, Proceedings of the National Academy of Sciences.

[2]  Benoit Landrein,et al.  Mechanical Stress Acts via Katanin to Amplify Differences in Growth Rate between Adjacent Cells in Arabidopsis , 2012, Cell.

[3]  A. Laughon,et al.  Expanded: a gene involved in the control of cell proliferation in imaginal discs. , 1993, Development.

[4]  Frank Jülicher,et al.  Fluidization of tissues by cell division and apoptosis , 2010, Proceedings of the National Academy of Sciences.

[5]  A. Kicheva,et al.  Morphogen gradient formation. , 2009, Cold Spring Harbor perspectives in biology.

[6]  N. Takahashi,et al.  Protocadherin LKC, a new candidate for a tumor suppressor of colon and liver cancers, its association with contact inhibition of cell proliferation. , 2002, Carcinogenesis.

[7]  Madhav Mani,et al.  Propagation of Dachsous-Fat Planar Cell Polarity , 2012, Current Biology.

[8]  G. Struhl,et al.  Recruitment of cells into the Drosophila wing primordium by a feed-forward circuit of vestigial autoregulation , 2007, Development.

[9]  Sirio Dupont.  Role of YAP/TAZ in mechanotransduction , 2011 .

[10]  S. Tsukita,et al.  Real-time imaging of cell-cell adherens junctions reveals that Drosophila mesoderm invagination begins with two phases of apical constriction of cells. , 2001, Journal of cell science.

[11]  Pedro Gaspar,et al.  Actin-Capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila , 2011, Journal of Cell Science.

[12]  Frank Jülicher,et al.  The Influence of Cell Mechanics, Cell-Cell Interactions, and Proliferation on Epithelial Packing , 2007, Current Biology.

[13]  D. Haber,et al.  salvador Promotes Both Cell Cycle Exit and Apoptosis in Drosophila and Is Mutated in Human Cancer Cell Lines , 2002, Cell.

[14]  Jennifer A Zallen,et al.  Patterned gene expression directs bipolar planar polarity in Drosophila. , 2004, Developmental cell.

[15]  Petros Koumoutsakos,et al.  Antagonistic growth regulation by Dpp and Fat drives uniform cell proliferation. , 2011, Developmental cell.

[16]  L. Sulak,et al.  Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation , 2004, Nature.

[17]  D. Fristrom,et al.  Apical cell shape changes during Drosophila imaginal leg disc elongation: a novel morphogenetic mechanism. , 1991, Development.

[18]  E. Coen,et al.  Generation of Leaf Shape Through Early Patterns of Growth and Tissue Polarity , 2012, Science.

[19]  A. Garcı́a-Bellido,et al.  Cell cycling and patterned cell proliferation in the wing primordium of Drosophila. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Hisao Honda,et al.  Planar Cell Polarity Links Axes of Spatial Dynamics in Neural-Tube Closure , 2012, Cell.

[21]  F Graner,et al.  Discrete rearranging disordered patterns, part I: Robust statistical tools in two or three dimensions , 2007, The European physical journal. E, Soft matter.

[22]  Philippe Marcq,et al.  Mechanical Control of Morphogenesis by Fat/Dachsous/Four-Jointed Planar Cell Polarity Pathway , 2012, Science.

[23]  T. Klein.  Immunolabeling of imaginal discs. , 2008, Methods in molecular biology.

[24]  Manuel Théry,et al.  The extracellular matrix guides the orientation of the cell division axis , 2005, Nature Cell Biology.

[25]  Jonathan E. Gale,et al.  Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding , 2012, Nature.

[26]  N. Perrimon,et al.  The emergence of geometric order in proliferating metazoan epithelia , 2006, Nature.

[27]  Pedro Gaspar,et al.  Actin-Capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila , 2011, Development.

[28]  David Strutt,et al.  Planar Polarity Specification through Asymmetric Subcellular Localization of Fat and Dachsous , 2012, Current Biology.

[29]  H. Nojima,et al.  Integration of morphogen signalling within the growth regulatory network. , 2012, Current opinion in cell biology.

[30]  Nicolas Minc,et al.  Influence of Cell Geometry on Division-Plane Positioning , 2011, Cell.

[31]  Pablo A. Iglesias,et al.  Mitosis-Specific Mechanosensing and Contractile-Protein Redistribution Control Cell Shape , 2006, Current Biology.

[32]  P. Bryant,et al.  A zone of non-proliferating cells at a lineage restriction boundary in Drosophila , 1985, Nature.

[33]  L. Mahadevan,et al.  Cell shape changes indicate a role for extrinsic tensile forces in Drosophila germ-band extension , 2009, Nature Cell Biology.

[34]  F. T. Lewis.  The effect of cell division on the shape and size of hexagonal cells , 1926 .

[35]  Jennifer A Zallen,et al.  Myosin II dynamics are regulated by tension in intercalating cells. , 2009, Developmental cell.

[36]  Jianbin Huang,et al.  The Hippo Signaling Pathway Coordinately Regulates Cell Proliferation and Apoptosis by Inactivating Yorkie, the Drosophila Homolog of YAP , 2005, Cell.

[37]  D. Fristrom,et al.  The mechanism of evagination of imaginal discs of Drosophila melanogaster. III. Evidence for cell rearrangement. , 1976, Developmental biology.

[38]  Masaaki Yoshigi,et al.  Mechanical force mobilizes zyxin from focal adhesions to actin filaments and regulates cytoskeletal reinforcement , 2005, The Journal of cell biology.

[39]  Yanlan Mao,et al.  Planar polarization of the atypical myosin Dachs orients cell divisions in Drosophila. , 2011, Genes & development.

[40]  N. Perrimon,et al.  Vector and parameters for targeted transgenic RNA interference in Drosophila melanogaster , 2008, Nature Methods.

[41]  Frank Jülicher,et al.  Increased Cell Bond Tension Governs Cell Sorting at the Drosophila Anteroposterior Compartment Boundary , 2009, Current Biology.

[42]  Michel Bornens,et al.  External forces control mitotic spindle positioning , 2011, Nature Cell Biology.

[43]  Radhika Nagpal,et al.  Control of the Mitotic Cleavage Plane by Local Epithelial Topology , 2011, Cell.

[44]  M. Mlodzik,et al.  Intertissue Mechanical Stress Affects Frizzled-Mediated Planar Cell Polarity in the Drosophila Notum Epidermis , 2011, Current Biology.

[45]  K. Irvine,et al.  Cooperative regulation of growth by Yorkie and Mad through bantam. , 2011, Developmental cell.

[46]  J. Dumais,et al.  Universal rule for the symmetric division of plant cells , 2011, Proceedings of the National Academy of Sciences.

[47]  A. Kicheva,et al.  Dynamics of Dpp Signaling and Proliferation Control , 2011, Science.

[48]  S. Eaton,et al.  Establishment of Global Patterns of Planar Polarity during Growth of the Drosophila Wing Epithelium , 2012, Current Biology.

[49]  Pierre-François Lenne,et al.  Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis , 2008, Nature Cell Biology.

[50]  G. Halder,et al.  Modulating F‐actin organization induces organ growth by affecting the Hippo pathway , 2011, The EMBO journal.

[51]  Thomas Lecuit,et al.  Orchestrating size and shape during morphogenesis , 2007, Nature.

[52]  Antonio Baonza,et al.  The Orientation of Cell Divisions Determines the Shape of Drosophila Organs , 2005, Current Biology.

[53]  Frank Jülicher,et al.  Cell Flow Reorients the Axis of Planar Polarity in the Wing Epithelium of Drosophila , 2010, Cell.

[54]  K. Irvine,et al.  Localization and requirement for Myosin II at the dorsal‐ventral compartment boundary of the Drosophila wing , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[55]  Yaopan Mao,et al.  Dachs: an unconventional myosin that functions downstream of Fat to regulate growth, affinity and gene expression in Drosophila , 2006, Development.

[56]  J. R. Kennaway,et al.  Genetic Control of Organ Shape and Tissue Polarity , 2010, PLoS biology.

[57]  C. Heisenberg,et al.  Forces in Tissue Morphogenesis and Patterning , 2013, Cell.

[58]  D. Fristrom,et al.  The mechanism of evagination of imaginal discs of Drosophila melanogaster. 1. General considerations. , 1975 .

[59]  G. Halder,et al.  Hippo signaling: growth control and beyond , 2011, Development.