Püschel A W, Balling R, Gruss P
Max-Planck-Institut für biophysikalische Chemie, Abteilung Molekulare Zellbiologie, Göttingen, FRG.
Development. 1991 May;112(1):279-87. doi: 10.1242/dev.112.1.279.
The Hox genes are a class of putative developmental control genes that are thought to be involved in the specification of positional identity along the anteroposterior axis of the vertebrate embryo. It is apparent from their expression pattern that their regulation is dependent upon positional information. In a previous analysis of the Hox-1.1 promoter in transgenic mice, we identified sequences that were sufficient to establish transgene expression in a specific region of the embryo. The construct used, however, did not contain enough regulatory sequences to reproduce all aspects of Hox-1.1 expression. In particular, neither a posterior boundary nor a restriction of expression to prevertebrae was achieved. Here we show correct regulation by Hox-1.1 sequences in transgenic mice and identify the elements responsible for different levels of control. Concomitant with the subdivision of mesodermal cells into different lineages during gastrulation and organogenesis, Hox-1.1 expression is restricted to successively smaller sets of cells. Distinct elements are required at different stages of development to execute this developmental programme. One position-responsive element (130 bp nontranslated leader) was shown to be crucial for the restriction of expression not only along the anteroposterior axis of the embryo, setting the posterior border, but also along the dorsoventral axis of the neural tube and to the lineage giving rise to the prevertebrae. Thus, Hox-1.1 expression is established in a specific region of the embryo and in a specific lineage of the mesoderm by restricting the activity of the promoter by the combined effect of several regulatory elements.
Hox基因是一类被认为参与脊椎动物胚胎前后轴位置身份特化的假定发育控制基因。从它们的表达模式可以明显看出，它们的调控依赖于位置信息。在之前对转基因小鼠中Hox-1.1启动子的分析中，我们鉴定出了足以在胚胎特定区域建立转基因表达的序列。然而，所使用的构建体并不包含足够的调控序列来重现Hox-1.1表达的所有方面。特别是，既没有实现后边界，也没有实现表达仅限于椎前体。在这里，我们展示了转基因小鼠中Hox-1.1序列的正确调控，并确定了负责不同控制水平的元件。在原肠胚形成和器官发生过程中，随着中胚层细胞分化为不同的谱系，Hox-1.1的表达仅限于越来越小的细胞群体。在发育的不同阶段需要不同的元件来执行这个发育程序。一个位置响应元件（130 bp非翻译前导序列）被证明不仅对于沿着胚胎前后轴限制表达、设定后边界至关重要，而且对于沿着神经管的背腹轴以及对于产生椎前体的谱系限制表达也至关重要。因此，通过几个调控元件的联合作用限制启动子的活性，Hox-1.1在胚胎的特定区域和中胚层的特定谱系中建立表达。
