Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Dev Cell. 2012 Mar 13;22(3):544-57. doi: 10.1016/j.devcel.2011.12.007. Epub 2012 Feb 16.
Patterning of the dorsal-ventral axis in the early Drosophila embryo depends on the nuclear distribution of the Dorsal transcription factor. Using live two-photon light-sheet microscopy, we quantified the nuclear Dorsal gradient in space and time and found that its amplitude and basal levels display oscillations throughout early embryonic development. These dynamics raise questions regarding how cells can reproducibly establish patterns of gene expression from a rapidly varying signal. We therefore quantified domains of Dorsal target genes, discovering their expression patterns are also dynamic. Computational modeling of this system reveals a correlation between Dorsal gradient dynamics and changes in target gene expression and suggests that these dynamics, together with time averaging of noise, results in the formation of graded gene expression borders in regions where the gradient is nearly flat. We propose that mRNA levels remain plastic during transient signaling events, allowing tissues to refine patterns in the face of genetic or environmental variation.
果蝇胚胎早期背腹轴的模式形成依赖于 Dorsal 转录因子的核分布。我们使用实时双光子光片显微镜定量分析了核 Dorsal 梯度在空间和时间上的分布，发现其幅度和基础水平在整个早期胚胎发育过程中都呈现出振荡。这些动态现象提出了一个问题，即细胞如何能够从快速变化的信号中重复地建立基因表达模式。因此，我们定量分析了 Dorsal 靶基因的表达区域，发现它们的表达模式也是动态的。对该系统的计算模型表明，Dorsal 梯度动态与靶基因表达的变化之间存在相关性，并表明这些动态以及噪声的时间平均作用，导致在梯度几乎平坦的区域形成梯度表达边界。我们提出，在短暂的信号事件中，mRNA 水平保持可塑性，使组织能够在面对遗传或环境变化时精细调整模式。
