Joseph Henry Laboratories of Physics and the Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Program in Biophysics, Harvard University, Cambridge, MA 02138, USA.
Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria.
Cell. 2019 Feb 7;176(4):844-855.e15. doi: 10.1016/j.cell.2019.01.007. Epub 2019 Jan 31.
In developing organisms, spatially prescribed cell identities are thought to be determined by the expression levels of multiple genes. Quantitative tests of this idea, however, require a theoretical framework capable of exposing the rules and precision of cell specification over developmental time. We use the gap gene network in the early fly embryo as an example to show how expression levels of the four gap genes can be jointly decoded into an optimal specification of position with 1% accuracy. The decoder correctly predicts, with no free parameters, the dynamics of pair-rule expression patterns at different developmental time points and in various mutant backgrounds. Precise cellular identities are thus available at the earliest stages of development, contrasting the prevailing view of positional information being slowly refined across successive layers of the patterning network. Our results suggest that developmental enhancers closely approximate a mathematically optimal decoding strategy.
在发育中的生物体中，空间规定的细胞身份被认为是由多个基因的表达水平决定的。然而，对这一观点的定量检验需要一个理论框架，该框架能够揭示细胞在发育过程中的规则和精度。我们以早期果蝇胚胎中的间隙基因网络为例，展示了如何将四个间隙基因的表达水平联合解码为位置的最佳指定，精度可达 1%。解码器无需任何自由参数即可正确预测不同发育时间点和各种突变背景下的配对规则表达模式的动态。因此，在发育的最早阶段就可以获得精确的细胞身份，这与位置信息在图案形成网络的连续层中逐渐细化的主流观点形成对比。我们的研究结果表明，发育增强子非常接近一种数学上最优的解码策略。
