Noise drives sharpening of gene expression boundaries in the zebrafish hindbrain

Molecular Systems Biology

Lei Zhang²  Kelly Radtke⁴  Likun Zheng²  Anna Q Cai¹  Thomas F Schilling³ 

[1] Department of Applied Mathematics, School of Mathematics and Statistics, University of New South Wales, Sydney, New South Wales, Australia;Department of Mathematics, University of California, Irvine, CA, USA;Center for Complex Biological Systems, University of California, Irvine, CA, USA;Department of Development and Cell Biology, University of California, Irvine, CA, USA

关键词: cellular decision;    intracellular noise;    morphogen;    signal transduction network;    stochastic fluctuation;   

DOI  :  10.1038/msb.2012.45

来源: Wiley

【 摘 要 】

Abstract

Morphogens provide positional information for spatial patterns of gene expression during development. However, stochastic effects such as local fluctuations in morphogen concentration and noise in signal transduction make it difficult for cells to respond to their positions accurately enough to generate sharp boundaries between gene expression domains. During development of rhombomeres in the zebrafish hindbrain, the morphogen retinoic acid (RA) induces expression of hoxb1a in rhombomere 4 (r4) and krox20 in r3 and r5. Fluorescent in situ hybridization reveals rough edges around these gene expression domains, in which cells co-express hoxb1a and krox20 on either side of the boundary, and these sharpen within a few hours. Computational analysis of spatial stochastic models shows, surprisingly, that noise in hoxb1a/krox20 expression actually promotes sharpening of boundaries between adjacent segments. In particular, fluctuations in RA initially induce a rough boundary that requires noise in hoxb1a/krox20 expression to sharpen. This finding suggests a novel noise attenuation mechanism that relies on intracellular noise to induce switching and coordinate cellular decisions during developmental patterning.

Synopsis

Fluctuations in morphogens often lead to gene expression domains with rough boundaries during development. A mechanism is described whereby intracellular noise can help coordinate cellular decisions during patterning and thereby sharpen expression boundaries.

• Fluorescent in situ hybridization reveals rough edges around gene expression domains during development of rhombomeres in the zebrafish hindbrain, in which cells co-express hoxb1a and krox20 on either side of a future boundary, and these domains sharpen within a few hours.
• Computational analysis of stochastic models demonstrates that the initial rough boundaries are caused by stochastic fluctuations in the morphogen, retinoic acid, which patterns the expression domains.
• Noise in gene expression induces switching between expression of one gene or the other to narrow the transition zone and enable sharpening of boundaries.

【 授权许可】

CC BY-NC-SA   
Copyright © 2012 EMBO and Macmillan Publishers Limited

Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.