Drosophila araucan and caupolican integrate intrinsic and signalling inputs for the acquisition by muscle progenitors of the lateral transverse fate.
Drosophila araucan and caupolican integrate intrinsic and signalling inputs for the acquisition by muscle progenitors of the lateral transverse fate.
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DOI：
10.1371/journal.pgen.1002186
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发表时间：
2011-07
期刊：
影响因子：
4.5
通讯作者：
Ruiz-Gómez M
中科院分区：
文献类型：
--
作者：
Carrasco-Rando M;Tutor AS;Prieto-Sánchez S;González-Pérez E;Barrios N;Letizia A;Martín P;Campuzano S;Ruiz-Gómez M
肌肉发生的一个中心问题是个体肌肉获得同一性。在果蝇中，当肌肉祖细胞被挑选出来时，它们已经表达了肌肉识别基因的独特组合。这种肌肉编码是位置和时间信号输入整合的结果。在这里，我们通过功能丧失和异位表达的方法，确定易洛魁复杂的同源框基因Araucan和culpolcan是新的肌肉识别基因，赋予横向肌肉识别能力。这种命运的获得需要阿劳肯/考波利肯抑制其他肌肉身份基因，如无精打采和退化。此外，我们还发现依赖于Caupolica的Slax表达依赖于Ras/Mitogen激活的蛋白激酶级联的激活状态。这为易洛魁基因整合在肌肉祖细胞中的方式提供了一个全面的洞察，信号输入调节基因表达和蛋白质活动。果蝇和脊椎动物一样，肌肉系统由不同类型的肌肉组成，这些肌肉必须与神经系统协调行动，以控制有机体正常运作所需的足够收缩力量的释放。因此，个体肌肉获得特定身份是肌肉系统生成的关键一步。在果蝇中，肌肉前体细胞(为成熟肌肉的形成提供种子的特定成肌细胞)整合了位置和时间信号输入，导致了肌肉识别基因的独特组合的表达，这赋予了它们特定的命运。到目前为止，对于这种整合是如何在分子水平上发生的，以及特定的密码如何翻译成特定的肌肉命运，人们知之甚少。在这里，我们表明，获得外侧横肌的命运需要由易洛魁复合体的两个同源蛋白Araucan和Caupolica介导，抑制其他肌肉识别基因，如slouch和vresgial。易洛魁蛋白的抑制或激活功能依赖于RAS信号通路的活性。因此，我们的工作将易洛魁基因置于一个节点，该节点整合信号输入并调节蛋白质活性和细胞命运决定。
A central issue of myogenesis is the acquisition of identity by individual muscles. In Drosophila, at the time muscle progenitors are singled out, they already express unique combinations of muscle identity genes. This muscle code results from the integration of positional and temporal signalling inputs. Here we identify, by means of loss-of-function and ectopic expression approaches, the Iroquois Complex homeobox genes araucan and caupolican as novel muscle identity genes that confer lateral transverse muscle identity. The acquisition of this fate requires that Araucan/Caupolican repress other muscle identity genes such as slouch and vestigial. In addition, we show that Caupolican-dependent slouch expression depends on the activation state of the Ras/Mitogen Activated Protein Kinase cascade. This provides a comprehensive insight into the way Iroquois genes integrate in muscle progenitors, signalling inputs that modulate gene expression and protein activity. In Drosophila, as in vertebrates, the muscular system consists of different types of muscles that must act in coordination with the nervous system to control the adequate release of contraction power required for the proper functioning of the organism. Therefore, the acquisition of specific identities by individual muscles is a key step in the generation of the muscular system. In Drosophila, muscle progenitors (specific myoblasts that seed the formation of mature muscles) integrate positional and temporal signalling inputs, resulting in the expression of unique combinations of muscle identity genes, which confer on them specific fates. Up to now, very little was known of how this integration takes place at a molecular level and how a particular code is translated into a specific muscle fate. Here we show that the acquisition of the lateral transverse muscle fate requires the repression mediated by Araucan and Caupolican, two homeoproteins of the Iroquois Complex, of other muscle identity genes, like slouch and vestigial. The repressor or activator function of the Iroquois proteins depends on the activity of the Ras signalling pathway. Therefore, our work places Iroquois genes at a nodal point that integrates signalling inputs and regulates protein activity and cell fate determination.
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影响因子：
56.9
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