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, QDate
2017-01Source Title
PLoS Computational BiologyPublisher
Public Library of Science (PLoS)University of Melbourne Author/s
HOLMES, WILLIAMAffiliation
School of Mathematics and StatisticsMetadata
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Journal ArticleCitations
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 AccessOpen Access at PMC
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5279720Abstract
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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