Bridging Decapentaplegic and Wingless signaling in Drosophila wings through repression of naked cuticle by Brinker
Bridging Decapentaplegic and Wingless signaling in Drosophila wings through repression of naked cuticle by Brinker
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Brinker 通过抑制裸露角质层桥接果蝇翅膀中的十肢瘫痪和无翼信号传导
DOI：
10.1242/dev.082578
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发表时间：
2013-01
期刊：
影响因子：
4.6
通讯作者：
Ming Fang
中科院分区：
文献类型：
--
作者：
Lin Yang;Fei Meng;Da Ma;Wei Xie;Ming Fang
Wnt和骨形态发生蛋白（BMP）是对动物发育中的各种事件至关重要的信号元件。在果蝇中，Wingless（Wg，Wnt配体）和Decapentaplegic（Dpp，BMP同源物）被认为通过不同的信号转导途径发挥作用，并独立地指导翅膀的图案化。然而，最近的研究表明，Mothers against Dpp（Mad），Dpp信号的关键转换器，可能是这两条通路之间的串扰节点，Mad在Wg信号中的积极和消极作用已被提出。在这里，我们描述了一种新的分子机制，Dpp信号抑制Wg输出。Brinker（Brk）是一种被Dpp下调的转录抑制因子，在体外和体内直接抑制裸角质层（nkd），其编码Wg信号传导的反馈抑制剂。通过遗传学研究，我们证明，Brk是所需的Wg靶基因表达在苍蝇翅膀成虫盘和翅膀发育过程中的Brk的损失或收益模仿损失或收益的Wg信号，分别。最后，我们表明Dpp正调控nkd的表达，负调控Wg靶基因Distal-less（Dll）。这些数据支持了一个模型，其中不同的信号通路通过负反馈机制相互作用。这种机制可以解释器官如何协调来自多种信号线索的输入。
Wnts and bone morphogenetic proteins (BMPs) are signaling elements that are crucial for a variety of events in animal development. In Drosophila, Wingless (Wg, a Wnt ligand) and Decapentaplegic (Dpp, a BMP homolog) are thought to function through distinct signal transduction pathways and independently direct the patterning of the wing. However, recent studies suggest that Mothers against Dpp (Mad), the key transducer of Dpp signaling, might serve as a node for the crosstalk between these two pathways, and both positive and negative roles of Mad in Wg signaling have been suggested. Here, we describe a novel molecular mechanism by which Dpp signaling suppresses Wg outputs. Brinker (Brk), a transcriptional repressor that is downregulated by Dpp, directly represses naked cuticle (nkd), which encodes a feedback inhibitor of Wg signaling, in vitro and in vivo. Through genetic studies, we demonstrate that Brk is required for Wg target gene expression in fly wing imaginal discs and that loss or gain of brk during wing development mimics loss or gain of Wg signaling, respectively. Finally, we show that Dpp positively regulates the expression of nkd and negatively regulates the Wg target gene Distal-less (Dll). These data support a model in which different signaling pathways interact via a negative-feedback mechanism. Such a mechanism might explain how organs coordinate inputs from multiple signaling cues.
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