Department of Biology, Texas A&M University, College Station, Texas 77843-3258, USA.
Dev Dyn. 2012 Jun;241(6):1062-75. doi: 10.1002/dvdy.23787. Epub 2012 Apr 25.
Vertebrate axis development depends upon wnt8a transcription in a dynamic pool of mesoderm progenitors at the posterior pole of the gastrulating embryo. The transcriptional mechanisms controlling wnt8a expression are not understood, but previous studies identified two phases of wnt8a expression in zebrafish: Nodal-dependent activation during early gastrulation (phase I) and No tail (Ntl)-dependent regulation from mid gastrula stages (phase II).
We identified two upstream cis-regulatory regions, proximal and distal, each of which possesses a promoter. The proximal regulatory region contains a margin-specific enhancer that is required for both the Nodal and Ntl responses. Phase I expression requires Nodal activation of the margin enhancer in combination with the transcription factor Zbtb4 and the distal regulatory region. Phase II expression requires Ntl regulation of the margin enhancer in the context of the proximal regulatory region. An additional mechanism is required to ensure the transition from phase I to phase II regulation. Analysis of stickleback wnt8a suggests this mechanism of regulation may be conserved.
The seemingly simple wnt8a expression pattern reflects complex interactions of multiple regulatory inputs.
脊椎动物轴的发育依赖于原肠胚形成胚胎后极部中胚层祖细胞中 wnt8a 的转录。控制 wnt8a 表达的转录机制尚不清楚，但先前的研究在斑马鱼中鉴定出 wnt8a 表达的两个阶段：早期原肠胚形成期间的 Nodal 依赖性激活（I 期）和从中肠胚阶段开始的 No tail（Ntl）依赖性调节（II 期）。
我们鉴定了两个上游顺式调控区，近端和远端，每个区域都有一个启动子。近端调控区包含一个边界特异性增强子，对于 Nodal 和 Ntl 反应都是必需的。I 期表达需要 Nodal 激活边界增强子与转录因子 Zbtb4 结合，并需要远端调控区。II 期表达需要 Ntl 在近端调控区的背景下调节边界增强子。需要一种额外的机制来确保从 I 期到 II 期调节的转变。刺鱼 wnt8a 的分析表明，这种调节机制可能是保守的。
看似简单的 wnt8a 表达模式反映了多种调控输入的复杂相互作用。
