Université Pierre et Marie Curie (Paris 6), UMR 7009 CNRS, Observatoire Océanologique, 06230 Villefranche-sur-mer, France.
Dev Biol. 2011 Sep 15;357(2):440-9. doi: 10.1016/j.ydbio.2011.07.005. Epub 2011 Jul 12.
The TGFβ family member Nodal is expressed early in the presumptive ventral ectoderm of the early sea urchin embryo and its activity is crucial for dorsal-ventral (D/V) axis specification. Analysis of the nodal promoter identified a number of critical binding sites for transcription factors of different families including Sox, Oct, TCF and bZIP, but in most cases the specific factors that regulate nodal expression are not known. In this study, we report that the maternal factor Oct1/2 functions as a positive regulator of nodal and that its activity is essential for the initiation of nodal expression. Inhibition of Oct1/2 mRNA translation produced embryos with severe axial defects similar to those observed following inhibition of Nodal function. We show that perturbing Oct1/2 function specifically disrupted specification of the ventral and dorsal ectodermal regions and that these effects were caused by the failure of nodal to be expressed early in development. Furthermore, we identified the key gene vg1/univin, which is also necessary for nodal expression, as an additional factor that was completely dependent on Oct1/2 for its zygotic expression. These data demonstrate that the maternal Oct1/2 protein plays an early and essential role in D/V axis specification by initiating the expression of nodal and vg1/univin, two genes that act at the top of the D/V ectoderm gene regulatory network.
TGFβ 家族成员 Nodal 早期在海胆胚胎的假定腹侧外胚层中表达,其活性对于背腹(D/V)轴特化至关重要。对 nodal 启动子的分析确定了许多关键的转录因子结合位点,这些转录因子来自不同的家族,包括 Sox、Oct、TCF 和 bZIP,但在大多数情况下,调节 nodal 表达的特定因子尚不清楚。在这项研究中,我们报告说母体因子 Oct1/2 作为 nodal 的正调控因子发挥作用,其活性对于 nodal 表达的起始是必需的。抑制 Oct1/2 mRNA 翻译会产生严重的轴向缺陷胚胎,类似于抑制 Nodal 功能后观察到的缺陷。我们表明,扰乱 Oct1/2 功能特异性地破坏了腹侧和背侧外胚层区域的特化,并且这些效应是由于 nodal 在早期发育中不能表达所致。此外,我们确定了关键基因 vg1/univin,它也是 nodal 表达所必需的,作为另外一个因子,其合子表达完全依赖于 Oct1/2。这些数据表明,母体 Oct1/2 蛋白通过启动 nodal 和 vg1/univin 的表达,在 D/V 轴特化中发挥早期和必需的作用,这两个基因在 D/V 外胚层基因调控网络的顶端起作用。