Department of Mathematics, University of California, Irvine, CA 92697-3875, USA.
Mol Syst Biol. 2012;8:613. doi: 10.1038/msb.2012.45.
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.
形态发生素为发育过程中基因表达的空间模式提供位置信息。然而，局部形态发生素浓度的随机波动和信号转导中的噪声等随机效应使得细胞难以准确地响应其位置，从而难以在基因表达域之间产生清晰的边界。在斑马鱼后脑的菱脑节发育过程中，形态发生素视黄酸 (RA) 诱导 hoxb1a 在菱脑节 4 (r4) 和 krox20 在 r3 和 r5 中的表达。荧光原位杂交显示这些基因表达域的边缘不平整，在边界的两侧细胞共表达 hoxb1a 和 krox20，并且在几个小时内边界变得更加清晰。对空间随机模型的计算分析令人惊讶地表明，hoxb1a/krox20 表达中的噪声实际上促进了相邻节段之间边界的锐化。具体来说，RA 的波动最初诱导出一个粗糙的边界，需要 hoxb1a/krox20 表达中的噪声来锐化。这一发现表明了一种新的噪声衰减机制，该机制依赖于细胞内噪声来诱导发育模式形成过程中的切换和协调细胞决策。
