42 research outputs found

    The spatiotemporal order of signaling events unveils the logic of development signaling

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    Motivation: Animals from worms and insects to birds and mammals show distinct body plans; however, the embryonic development of diverse body plans with tissues and organs within is controlled by a surprisingly few signaling pathways. It is well recognized that combinatorial use of and dynamic interactions among signaling pathways follow specific logic to control complex and accurate developmental signaling and patterning, but it remains elusive what such logic is, or even, what it looks like. Results: We have developed a computational model for Drosophila eye development with innovated methods to reveal how interactions among multiple pathways control the dynamically generated hexagonal array of R8 cells. We obtained two novel findings. First, the coupling between the long-range inductive signals produced by the proneural Hh signaling and the short-range restrictive signals produced by the antineural Notch and EGFR signaling is essential for generating accurately spaced R8s. Second, the spatiotemporal orders of key signaling events reveal a robust pattern of lateral inhibition conducted by Ato-coordinated Notch and EGFR signaling to collectively determine R8 patterning. This pattern, stipulating the orders of signaling and comparable to the protocols of communication, may help decipher the well-appreciated but poorly-defined logic of developmental signaling

    Hybrid cell centred/vertex model for large tissue deformations

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    Macroscopic deformations in embryonic soft tissues are due to the intra-cellular remodelling and cell intercalation. We here present a computational approach that can handle the two types of deformations, and also take into account the active cell response. The model resorts to cell-centred techniques, where particles represent cell nuclei, and to vertex models, where the vertices represent cell boundaries. This hybrid approach allows to consider separately intracellular and inter-cellular forces, and at the same time impose cell incompressibility. In the proposed model, the cell boundaries (defined by vertices) and cell nuclei (or cellcentres) networks are coupled through an interpolation scheme, which is eventually relaxed in order to smooth the cell boundaries. We show that this coupling between the two networks modifies the equilibrium equations and stabilises the vertex network. Incompressibility is implemented through a penalty method. The resulting model can be implemented in two- and three-dimensions, and is complemented with active rheological models. We apply the model to simulate the stretching and relaxation of cell monolayers, and to simulate wound healing process in the wing disc of Drosophila fly embryo. We show that the numerical results agree with the experimental measurements.Postprint (published version

    Tissue Mechanics Regulate Mitotic Nuclear Dynamics during Epithelial Development.

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    Cell divisions are essential for tissue growth. In pseudostratified epithelia, where nuclei are staggered across the tissue, each nucleus migrates apically before undergoing mitosis. Successful apical nuclear migration is critical for planar-orientated cell divisions in densely packed epithelia. Most previous investigations have focused on the local cellular mechanisms controlling nuclear migration. Inter-species and inter-organ comparisons of different pseudostratified epithelia suggest global tissue architecture may influence nuclear dynamics, but the underlying mechanisms remain elusive. Here, we use the developing Drosophila wing disc to systematically investigate, in a single epithelial type, how changes in tissue architecture during growth influence mitotic nuclear migration. We observe distinct nuclear dynamics at discrete developmental stages, as epithelial morphology changes. We use genetic and physical perturbations to show a direct effect of cell density on mitotic nuclear positioning. We find Rho kinase and Diaphanous, which facilitate mitotic cell rounding in confined cell conditions, are essential for efficient apical nuclear movement. Perturbation of Diaphanous causes increasing defects in apical nuclear migration as the tissue grows and cell density increases, and these defects can be reversed by acute physical reduction of cell density. Our findings reveal how the mechanical environment imposed on cells within a tissue alters the molecular and cellular mechanisms adopted by single cells for mitosis

    Fundamental physical cellular constraints drive self-organization of tissues

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    Morphogenesis is driven by small cell shape changes that modulate tissue organization. Apical surfaces of proliferating epithelial sheets have been particularly well studied. Currently, it is accepted that a stereotyped distribution of cellular polygons is conserved in proliferating tissues among metazoans. In this work, we challenge these previous findings showing that diverse natural packed tissues have very different polygon distributions. We use Voronoi tessellations as a mathematical framework that predicts this diversity. We demonstrate that Voronoi tessellations and the very different tissues analysed share an overriding restriction: the frequency of polygon types correlates with the distribution of cell areas. By altering the balance of tensions and pressures within the packed tissues using disease, genetic or computer model perturbations, we show that as long as packed cells present a balance of forces within tissue, they will be under a physical constraint that limits its organization. Our discoveries establish a new framework to understand tissue architecture in development and disease. Synopsis Cell shapes in naturally packed tissues have different polygon distributions. Voronoi tessellations-based analysis suggests that polygon frequencies are restricted by the distribution of cell areas, and that this restriction emanates from the balance of forces within the tissue. Cell shapes in natural packed tissues present very different polygon distributions. These patterns can be reproduced by Voronoi tessellations. Natural tissues and Voronoi diagrams share some geometrical properties. There is a physical constraint that limits the organization of natural tissues. Unbalance of forces within the natural tissue breaks this restriction. Cell shapes in naturally packed tissues have different polygon distributions. Voronoi tessellations-based analysis suggests that polygon frequencies are restricted by the distribution of cell areas, and that this restriction emanates from the balance of forces within the tissue.Ministerio de Ciencia e Innovación BFU2011-2573

    EpiTools : an open-source image analysis toolkit for quantifying epithelial growth dynamics

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    Epithelia grow and undergo extensive rearrangements to achieve their final size and shape. Imaging the dynamics of tissue growth and morphogenesis is now possible with advances in time-lapse microscopy, but a true understanding of their complexities is limited by automated image analysis tools to extract quantitative data. To overcome such limitations, we have designed a new open-source image analysis toolkit called EpiTools. It provides user-friendly graphical user interfaces for accurately segmenting and tracking the contours of cell membrane signals obtained from 4D confocal imaging. It is designed for a broad audience, especially biologists with no computer-science background. Quantitative data extraction is integrated into a larger bioimaging platform, Icy, to increase the visibility and usability of our tools. We demonstrate the usefulness of EpiTools by analyzing Drosophila wing imaginal disc growth, revealing previously overlooked properties of this dynamic tissue, such as the patterns of cellular rearrangements

    EpiGraph: an open-source platform to quantify epithelial organization

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    Here we present EpiGraph, an image analysis tool that quantifies epithelial organization. Our method combines computational geometry and graph theory to measure the degree of order of any packed tissue. EpiGraph goes beyond the traditional polygon distribution analysis, capturing other organizational traits that improve the characterization of epithelia. EpiGraph can objectively compare the rearrangements of epithelial cells during development and homeostasis to quantify how the global ensemble is affected. Importantly, it has been implemented in the open-access platform Fiji. This makes EpiGraph very user friendly, with no programming skills required.España Ministerio de Economia, Industria y Competitividad BFU2016-74975-PEspaña, Programa Ramón y Cajal (PI13/ 01347

    Modulation of Drosophila Retinal Epithelial Integrity by the Adhesion Proteins Capricious and Tartan

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    Background The development of the Drosophila eye imaginal disc requires complex epithelial rearrangements. Cells of the morphogenetic furrow are apically constricted and this leads to a physical indentation in the epithelium. Posterior to the furrow, cells start to rearrange into distinct clusters and eventually form a precisely patterned array of ommatidia. These morphogenetic processes include regulated changes of adhesion between cells. Methodology/Principal Findings Here, we show that two transmembrane adhesion proteins, Capricious and Tartan, have dynamic and complementary expression patterns in the eye imaginal disc. We also describe novel null mutations in capricious and double null mutations in capricious and tartan. We report that they have redundant functions in regulating the architecture of the morphogenetic furrow and ommatidial spacing. Conclusions/Significance We conclude that Capricious and Tartan contribute to the adhesive properties of the cells in the morphogenetic furrow and that this regulated adhesion participates in the control of spacing ommatidial clusters

    Bibliometric study on three journals of electronic commerce.

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    In this dissertation, the publication patterns of three electronic commerce journals, namely, the International Journal of Electronic Commerce (IJEC), Electronic Commerce Research and Applications (ECRA), and the Journal of Organizational Computing and Electronic Commerce (JOCEC) were studied. Five years of bibliometric information, from 2004 to 2008, were retrieved from the Web of Science database, and to ensure accuracy, the records were counter-checked with those the ScienceDirect database. They were then analysed using the Microsoft Excel spreadsheet. In terms of annual publication counts, ECRA has the most (154 articles) articles. It is followed by IJEC (110 articles), and JOCEC (74 articles.). ECRA is the most consistent in terms of the mode authorship and it has a mode of two authors per article over each of the five years. JOCEC has a mode of two authors for 2004, 2005 and 2006, and a mode of three authors per paper for the 2006, 2007 and 2008. IJEC has a mode of two authors per paper for 2004, 2005 and 2008, and a mode of three authors per paper for 2006 and 2007. The extent of collaboration in each journal was determined using their collaborative index (CI), degree of collaboration (DC) and collaborative coefficient (CC). CI values ranged from 2.38 to 2.63, DC from 0.85 to 0.88, and CC from 0.50 to 0. 53. This indicates that there were no significant changes in the extent of collaboration over the five years. These results were also compared with those published by other researchers in the areas of business and computer science. Lastly, the prolific authors for each of the journals were identified and ranked using three measures, whole counting, fractional counting, and first-author counting. An overwhelming majority of the prolific authors worked in the United States, which is unsurprising, given that e-commerce first took hold in there.Master of Science (Knowledge Management
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