Developmental Cell ( IF 11.8 ) Pub Date : 2020-08-05 , DOI: 10.1016/j.devcel.2020.07.007 Caroline Hoppe 1 , Jonathan R Bowles 1 , Thomas G Minchington 1 , Catherine Sutcliffe 1 , Priyanka Upadhyai 1 , Magnus Rattray 1 , Hilary L Ashe 1
Morphogen gradients specify cell fates during development, with a classic example being the bone morphogenetic protein (BMP) gradient’s conserved role in embryonic dorsal-ventral axis patterning. Here, we elucidate how the BMP gradient is interpreted in the Drosophila embryo by combining live imaging with computational modeling to infer transcriptional burst parameters at single-cell resolution. By comparing burst kinetics in cells receiving different levels of BMP signaling, we show that BMP signaling controls burst frequency by regulating the promoter activation rate. We provide evidence that the promoter activation rate is influenced by both enhancer and promoter sequences, whereas Pol II loading rate is primarily modulated by the enhancer. Consistent with BMP-dependent regulation of burst frequency, the numbers of BMP target gene transcripts per cell are graded across their expression domains. We suggest that graded mRNA output is a general feature of morphogen gradient interpretation and discuss how this can impact on cell-fate decisions.
中文翻译:
启动子激活率的调节决定了果蝇胚胎中对分级 BMP 信号水平的转录反应。
形态发生梯度指定细胞在发育过程中的命运,一个典型的例子是骨形态发生蛋白(BMP)梯度在胚胎背腹轴模式中的保守作用。在这里,我们通过将实时成像与计算模型相结合来推断单细胞分辨率的转录爆发参数,阐明了如何在果蝇胚胎中解释 BMP 梯度。通过比较接受不同水平 BMP 信号传导的细胞中的爆发动力学,我们表明 BMP 信号传导通过调节启动子激活速率来控制爆发频率。我们提供的证据表明启动子激活率同时受到增强子和启动子序列的影响,而 Pol II 加载率主要受增强子调节。与 BMP 依赖性突发频率调节一致,每个细胞的 BMP 靶基因转录本数量在其表达域中分级。我们认为分级 mRNA 输出是形态发生素梯度解释的一般特征,并讨论这如何影响细胞命运的决定。