Publications by authors named "Simon Restrepo"

Previous studies have identified topologically associating domains (TADs) as basic units of genome organization. We present evidence of a previously unreported level of genome folding, where distant TAD pairs, megabases apart, interact to form meta-domains. Within meta-domains, gene promoters and structural intergenic elements present in distant TADs are specifically paired.

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Boundaries in animal genomes delimit contact domains with enhanced internal contact frequencies and have debated functions in limiting regulatory cross-talk between domains and guiding enhancers to target promoters. Most mammalian boundaries form by stalling of chromosomal loop-extruding cohesin by CTCF, but most boundaries form CTCF independently. However, how CTCF-independent boundaries form and function remains largely unexplored.

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The ex vivo cultivation and live imaging of wing discs open exciting new research avenues by overcoming the limitations of end-point analysis of fixed tissues. Here we describe how to prepare an optimized wing disc culture medium (WM1) and how to dissect and arrange wing discs for cultivation and live imaging. This protocol enables the study of dynamic phenomena such as cell division and delamination as well as the use of pharmacological compounds and biosensors.

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Calcium signalling is a highly versatile cellular communication system that modulates basic functions such as cell contractility, essential steps of animal development such as fertilization and higher-order processes such as memory. We probed the function of calcium signalling in Drosophila wing imaginal discs through a combination of ex vivo and in vivo imaging and genetic analysis. Here we discover that wing discs display slow, long-range intercellular calcium waves (ICWs) when mechanically stressed in vivo or cultured ex vivo.

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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.

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The elegance of animal body plans derives from an intimate connection between function and form, which during organ formation is linked to patterning and growth. Yet, how patterning and growth are coordinated still remains largely a mystery. To study this question the Drosophila wing imaginal disc, an epithelial primordial organ that later forms the adult wing, has proven to be an invaluable and versatile model.

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The Drosophila wing imaginal disc is a key model organ for molecular developmental genetics. Wing disc studies are generally restricted to end-point analyses of fixed tissues. Recently several studies have relied on limited data from discs cultured in uncharacterized conditions.

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Wartlick et al. (Research Articles, 4 March 2011, p. 1154) reported that growth rates in the Drosophila wing disc correlate with increasing Dpp signaling levels, suggesting that the rate of Dpp increase determines the cell-cycle length.

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An expansion-repression mechanism by which morphogen gradients can adjust to size and growth had been postulated as a model. Now, its molecular nature has been uncovered.

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Morphogens can control organ development by regulating patterning as well as growth. Here we use the model system of the Drosophila wing imaginal disc to address how the patterning signal Decapentaplegic (Dpp) regulates cell proliferation. Contrary to previous models, which implicated the slope of the Dpp gradient as an essential driver of cell proliferation, we find that the juxtaposition of cells with differential pathway activity is not required for proliferation.

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