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首页> 外文期刊>Development >Activin receptor inhibition by Smad2 regulates Drosophila wing disc patterning through BMP-response elements
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Activin receptor inhibition by Smad2 regulates Drosophila wing disc patterning through BMP-response elements

机译：Smad2对激活素受体的抑制作用通过BMP响应元件调节果蝇翼盘模式。

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摘要

Imaginal disc development in Drosophila requires coordinated cellular proliferation and tissue patterning. In our studies of TGFβ superfamily signaling components, we found that a protein null mutation of Smad2, the only Activin subfamily R-Smad in the fruit fly, produces overgrown wing discs that resemble gain of function for BMP subfamily signaling. The wing discs are expanded specifically along the anterior-posterior axis, with increased proliferation in lateral regions. The morphological defect is not observed in mutants for the TGFβ receptor baboon, and epistasis tests showed that baboon is epistatic to Smad2 for disc overgrowth. Rescue experiments indicate that Baboon binding, but not canonical transcription factor activity, of Smad2 is required for normal disc growth. Smad2 mutant discs generate a P-Mad stripe that is narrower and sharper than the normal gradient, and activation targets are correspondingly expressed in narrowed domains. Repression targets of P-Mad are profoundly mis-regulated, with brinker and pentagone reporter expression eliminated in Smad2 mutants. Loss of expression requires a silencer element previously shown to be controlled by BMP signaling. Epistasis experiments show that Baboon, Mad and Schnurri are required to mediate the ectopic silencer output in the absence of Smad2. Taken together, our results show that loss of Smad2 permits promiscuous Baboon activity, which represses genes subject to control by Mad-dependent silencer elements. The absence of Brinker and Pentagone in Smad2 mutants explains the compound wing disc phenotype. Our results highlight the physiological relevance of substrate inhibition of a kinase, and reveal a novel interplay between the Activin and BMP pathways.
机译：果蝇的想象中的椎间盘发育需要协调的细胞增殖和组织模式。在我们对TGFβ超家族信号传导成分的研究中，我们发现果蝇中唯一的激活素亚家族R-Smad的Smad2蛋白无效突变产生了类似于BMP亚家族信号传导功能增强的机翼圆盘。翅片专门沿前后轴扩张，在侧面区域增生。在TGFβ受体狒狒的突变体中未观察到形态缺陷，并且上位性测试表明，对于圆盘过度生长，狒狒向Smad2上位。救援实验表明，正常椎间盘的生长需要Smad2的狒狒结合而不是规范的转录因子活性。 Smad2突变体光盘生成的P-Mad条纹比正常梯度更窄和更锐利，并且激活目标在狭窄域中相应表达。对P-Mad的抑制目标进行了严重的错误调节，消除了Smad2突变体中的皱纹和五肽酮报告基因表达。表达的丧失要求消音器元件先前显示受BMP信号控制。上位性实验表明，在不存在Smad2的情况下，需要狒狒，Mad和Schnurri介导异位沉默子的输出。两者合计，我们的结果表明，Smad2的丢失允许混杂的狒狒活动，它抑制受Mad依赖的沉默子元件控制的基因。 Smad2突变体中不存在Brinker和Pentagone可以解释复合翼盘表型。我们的结果突出了底物抑制激酶的生理相关性，并揭示了激活素和BMP途径之间的新型相互作用。

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