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    Cell Sorting and Noise-Induced Cell Plasticity Coordinate to Sharpen Boundaries between Gene Expression Domains.

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    Author
    Wang, Q; Holmes, WR; Sosnik, J; Schilling, T; Nie, Q
    Date
    2017-01
    Source Title
    PLoS Computational Biology
    Publisher
    Public Library of Science (PLoS)
    University of Melbourne Author/s
    HOLMES, WILLIAM
    Affiliation
    School of Mathematics and Statistics
    Metadata
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    Document Type
    Journal Article
    Citations
    Wang, Q., Holmes, W. R., Sosnik, J., Schilling, T. & Nie, Q. (2017). Cell Sorting and Noise-Induced Cell Plasticity Coordinate to Sharpen Boundaries between Gene Expression Domains.. PLoS Comput Biol, 13 (1), pp.e1005307-. https://doi.org/10.1371/journal.pcbi.1005307.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255785
    DOI
    10.1371/journal.pcbi.1005307
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5279720
    Abstract
    A fundamental question in biology is how sharp boundaries of gene expression form precisely in spite of biological variation/noise. Numerous mechanisms position gene expression domains across fields of cells (e.g. morphogens), but how these domains are refined remains unclear. In some cases, domain boundaries sharpen through differential adhesion-mediated cell sorting. However, boundaries can also sharpen through cellular plasticity, with cell fate changes driven by up- or down-regulation of gene expression. In this context, we have argued that noise in gene expression can help cells transition to the correct fate. Here we investigate the efficacy of cell sorting, gene expression plasticity, and their combination in boundary sharpening using multi-scale, stochastic models. We focus on the formation of hindbrain segments (rhombomeres) in the developing zebrafish as an example, but the mechanisms investigated apply broadly to many tissues. Our results indicate that neither sorting nor plasticity is sufficient on its own to sharpen transition regions between different rhombomeres. Rather the two have complementary strengths and weaknesses, which synergize when combined to sharpen gene expression boundaries.

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