Comparative analysis of Hox downstream genes in Drosophila
Comparative analysis of Hox downstream genes in Drosophila
复制标题
DOI：
10.1242/dev.02746
复制
发表时间：
2007-01-15
期刊：
影响因子：
4.6
通讯作者：
Lohmann, Ingrid
中科院分区：
文献类型：
--
作者：
Hueber, Stefanie D.;Bezdan, Daniela;Lohmann, Ingrid
身体各部分功能的多样化依赖于沿着不同身体轴沿着的专门结构的形成。在动物中，沿前后轴的区域特异性形态发生沿着由Hox基因编码的一组保守的转录因子控制。虽然长期以来一直认为Hox蛋白通过调节不同的下游基因组来发挥其功能，但只有少数这样的基因被发现，很少有直接控制细胞行为的作用。我们已经通过微阵列分析定量鉴定了果蝇中数百个Hox下游基因，并通过对功能丧失和获得突变体的原位杂交验证了其中许多基因。一个重要的发现是，Hox蛋白尽管在体外具有相似的DNA结合特性，但对体内转录组具有高度特异性的影响，因为许多下游基因的表达主要响应单个Hox蛋白。此外，大部分下游基因编码实现子功能，其直接影响形态发生过程，例如细胞分裂的方向和速率、细胞-细胞粘附和通信、细胞形状和迁移或细胞死亡。集中在这些实现者，我们提供了一个框架的上颌段的形态发生。由于Hox基因的基因组结构和Hox蛋白与特定辅因子的相互作用在脊椎动物和无脊椎动物中是保守的，并且类似类别的下游基因受Hox蛋白在后生动物生殖发育中的调控，我们的研究结果代表了对物种内以及物种之间形态多样化的机械理解的第一步。
Functional diversification of body parts is dependent on the formation of specialized structures along the various body axes. In animals, region-specific morphogenesis along the anteroposterior axis is controlled by a group of conserved transcription factors encoded by the Hox genes. Although it has long been assumed that Hox proteins carry out their function by regulating distinct sets of downstream genes, only a small number of such genes have been found, with very few having direct roles in controlling cellular behavior. We have quantitatively identified hundreds of Hox downstream genes in Drosophila by microarray analysis, and validated many of them by in situ hybridizations on loss- and gain-of-function mutants. One important finding is that Hox proteins, despite their similar DNA-binding properties in vitro, have highly specific effects on the transcriptome in vivo, because expression of many downstream genes respond primarily to a single Hox protein. In addition, a large fraction of downstream genes encodes realizator functions, which directly affect morphogenetic processes, such as orientation and rate of cell divisions, cell-cell adhesion and communication, cell shape and migration, or cell death. Focusing on these realizators, we provide a framework for the morphogenesis of the maxillary segment. As the genomic organization of Hox genes and the interaction of Hox proteins with specific co-factors are conserved in vertebrates and invertebrates, and similar classes of downstream genes are regulated by Hox proteins across the metazoan phylogeny, our findings represent a first step toward a mechanistic understanding of morphological diversification within a species as well as between species.