Conversion of an extracellular Dpp/BMP morphogen gradient into an inverse transcriptional gradient
Conversion of an extracellular Dpp/BMP morphogen gradient into an inverse transcriptional gradient
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DOI：
10.1016/s0092-8674(03)00241-1
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发表时间：
2003-04-18
期刊：
影响因子：
64.5
通讯作者：
Basler, K
中科院分区：
文献类型：
--
作者：
Müller, B;Hartmann, B;Basler, K
形态梯度通过差异调节细胞行为来控制体型。在这里，我们分析的DPP/BMP形态发生在果蝇的主要反应的分子事件。在整个发育过程中，Dpp转导导致brinker（brk）基因的分级转录下调。我们首先提供的brk表达梯度的意义表明，不同的Brk水平抑制不同的组合翼基因表达在不同的距离DPP分泌细胞。然后，我们解剖的brk调控区，并确定两个可分离的元素具有相反的属性，一个组成性增强子和DPP形态发生调节沉默。此外，我们目前的遗传和生化证据表明，作为一个直接目标的蛋白质复合物组成的Smad同系物疯狂/美狄亚和锌指蛋白Schnurri的brk沉默。总之，我们的研究结果提供了一个机制，细胞外Dpp/BMP形态形成建立一个微调，分级读出转录抑制的分子框架。
Morphogen gradients control body pattern by differentially regulating cellular behavior. Here, we analyze the molecular events underlying the primary response to the Dpp/BMP morphogen in Drosophila. Throughout development, Dpp transduction causes the graded transcriptional downregulation of the brinker (brk) gene. We first provide significance for the brk expression gradient by showing that different Brk levels repress distinct combinations of wing genes expressed at different distances from Dpp-secreting cells. We then dissect the brk regulatory region and identify two separable elements with opposite properties, a constitutive enhancer and a Dpp morphogen-regulated silencer. Furthermore, we present genetic and biochemical evidence that the brk silencer serves as a direct target for a protein complex consisting of the Smad homologs Mad/Medea and the zinc finger protein Schnurri. Together, our results provide the molecular framework for a mechanism by which the extracellular Dpp/BMP morphogen establishes a finely tuned, graded read-out of transcriptional repression.