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PLoS Comput Biol. 2017 Jan 30;13(1):e1005307. doi: 10.1371/journal.pcbi.1005307. eCollection 2017 Jan.

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

Author information

1
Center for Complex Biological Systems, University of California Irvine, Irvine, CA, United States of America.
2
Department of Mathematics, University of California Irvine, Irvine, CA, United States of America.
3
Department of Physics and Astronomy, Vanderbilt University, Nashville, TN, United States of America.
4
Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA, United States of America.

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.

PMID:
28135279
PMCID:
PMC5279720
DOI:
10.1371/journal.pcbi.1005307
[Indexed for MEDLINE]
Free PMC Article

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