title: Cell Sorting and Noise-Induced Cell Plasticity Coordinate to Sharpen Boundaries between Gene Expression Domains.
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.
authors.affiliation: Center for Complex Biological Systems, University of California Irvine, Irvine, CA, United States of America.|Department of Mathematics, University of California Irvine, Irvine, CA, United States of America.
authors.forename: Qixuan
authors.identifier: 0000-0003-4511-6843
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Physics and Astronomy, Vanderbilt University, Nashville, TN, United States of America.
authors.forename: William R
authors.identifier: 0000-0003-4511-6843
authors.initials: WR
authors.lastname: Holmes
authors.affiliation: Center for Complex Biological Systems, University of California Irvine, Irvine, CA, United States of America.|Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA, United States of America.
authors.forename: Julian
authors.identifier: 0000-0002-0528-9929
authors.initials: J
authors.lastname: Sosnik
authors.affiliation: Center for Complex Biological Systems, University of California Irvine, Irvine, CA, United States of America.|Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA, United States of America.
authors.forename: Thomas
authors.identifier: 0000-0003-1798-8695
authors.initials: T
authors.lastname: Schilling
authors.affiliation: Center for Complex Biological Systems, University of California Irvine, Irvine, CA, United States of America.|Department of Mathematics, University of California Irvine, Irvine, CA, United States of America.
authors.forename: Qing
authors.identifier: 0000-0002-8804-3368
authors.initials: Q
authors.lastname: Nie
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement; D015870:Gene Expression / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D008954:Models, Biological; D015233:Models, Statistical; D009024:Morphogenesis; D054259:Neural Tube / Q000166:cytology* / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D012249:Rhombencephalon / Q000166:cytology / Q000502:physiology; D059629:Signal-To-Noise Ratio; D013269:Stochastic Processes; D015027:Zebrafish