Mad is required for wingless signaling in wing development and segment patterning in Drosophila.
Mad is required for wingless signaling in wing development and segment patterning in Drosophila.
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DOI：
10.1371/journal.pone.0006543
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发表时间：
2009-08-06
期刊：
影响因子：
3.7
通讯作者：
De Robertis EM
中科院分区：
文献类型：
--
作者：
Eivers E;Fuentealba LC;Sander V;Clemens JC;Hartnett L;De Robertis EM
发育生物学的一个关键问题是生长因子信号如何整合以生成模式。在这项研究中，我们通过转录因子 Mad 的磷酸化研究了果蝇 BMP 和 Wingless/GSK3 信号通路的整合。 Wingless 被发现可以在体内调节 GSK3 对 Mad 的磷酸化。在上位实验中，Wingless 对翼盘分子标记（无意义、远端和退化）的影响通过 RNAi 消耗 Mad 来抑制。 Mad GSK3 磷酸化抗性突变蛋白诱导无翅过度表达表型，例如异位翅边缘的形成。出乎意料的是，我们发现GSK3和MAPK的Mad磷酸化以节段模式发生。疯狂耗竭或过度表达产生无翅样胚胎分割表型。在非洲爪蟾胚胎中，节段边界的形成因 Smad8 缺失而被破坏。结果表明，Mad 是 Wingless 信号传递和位置信息梯度整合所必需的。
A key question in developmental biology is how growth factor signals are integrated to generate pattern. In this study we investigated the integration of the Drosophila BMP and Wingless/GSK3 signaling pathways via phosphorylations of the transcription factor Mad. Wingless was found to regulate the phosphorylation of Mad by GSK3 in vivo. In epistatic experiments, the effects of Wingless on wing disc molecular markers (senseless, distalless and vestigial) were suppressed by depletion of Mad with RNAi. Wingless overexpression phenotypes, such as formation of ectopic wing margins, were induced by Mad GSK3 phosphorylation-resistant mutant protein. Unexpectedly, we found that Mad phosphorylation by GSK3 and MAPK occurred in segmental patterns. Mad depletion or overexpression produced Wingless-like embryonic segmentation phenotypes. In Xenopus embryos, segmental border formation was disrupted by Smad8 depletion. The results show that Mad is required for Wingless signaling and for the integration of gradients of positional information.
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