Coordinated control of cell adhesion, polarity, and cytoskeleton underlies Hox-induced organogenesis in Drosophila

Coordinated control of cell adhesion, polarity, and cytoskeleton underlies Hox-induced organogenesis in Drosophila
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DOI:
10.1016/j.cub.2006.09.029
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发表时间:
2006-11-21
期刊:
影响因子:
9.2
通讯作者:
Castelli-Gair Hombria, James
Castelli-Gair Hombria, James
中科院分区:
生物学1区
文献类型:
--
作者:
Lovegrove, Bridget;Simoes, Sergio;Castelli-Gair Hombria, James

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背景:Hox基因通过指导节段特异性结构的形态发生来控制动物的身体计划。作为转录因子,HOX蛋白通过激活下游靶基因来实现这一点。大量的研究已经致力于寻找这些目标和表征它们在器官发生中的作用。这表明Hox激活的直接靶点通常是转录因子或信号分子,它们形成指导特定器官形态发生的分级遗传网络。重要的是,很少有直接的Hox目标已知的是“realizator”基因直接参与的细胞过程的organogenesis. Results:在这里,我们描述了第一次一个完整的网络连接的Hox基因腹部-B的realizator基因,它控制在器官发育的幼虫的外部呼吸器官。在这个过程中,Abdominal-B诱导四个中间信号分子和转录因子的表达,并且这种表达导致几个实现基因的嵌合激活。ABD-B气门实现因子包括至少五种细胞粘附蛋白、细胞极性蛋白以及GAP和GEF细胞骨架调节因子。同时异位表达的Abd-B下游的目标可以诱导spiracle样结构的形成在ABD-B protein.Conclusion的情况下:Hox realizators包括细胞骨架调节剂和所需的顶基底细胞组织的分子。HOX协调激活这些实现马赛克模式赋予器官原基其组装性能。我们提出,在动物发育过程中,Hox控制的遗传级联协调局部细胞特异性行为,导致器官发生的片段特异性结构。
Background: Hox genes control animal body plans by directing the morphogenesis of segment-specific structures. As transcription factors, HOX proteins achieve this through the activation of downstream target genes. Much research has been devoted to the search for these targets and the characterization of their roles in organogenesis. This has shown that the direct targets of Hox activation are often transcription factors or signaling molecules, which form hierarchical genetic networks directing the morphogenesis of particular organs. Importantly, very few of the direct Hox targets known are "realizator" genes involved directly in the cellular processes of organogenesis.Results: Here, we describe for the first time a complete network linking the Hox gene Abdominal-B to the realizator genes it controls during the organogenesis of the external respiratory organ of the larva. In this process, Abdominal-B induces the expression of four intermediate signaling molecules and transcription factors, and this expression results in the mosaic activation of several realizator genes. The ABD-B spiracle realizators; include at least five cell-adhesion proteins, cell-polarity proteins, and GAP and GEF cytoskeleton regulators. Simultaneous ectopic expression of the Abd-B downstream targets can induce spiracle-like structure formation in the absence of ABD-B protein.Conclusion: Hox realizators include cytoskeletal regulators and molecules required for the apico-basal cell organization. HOX-coordinated activation of these realizators in mosaic patterns confers to the organ primordium its assembling properties. We propose that during animal development, Hox-controlled genetic cascades coordinate the local cell-specific behaviors that result in organogenesis of segment-specific structures.