MRC Centre for Developmental & Biomedical Genetics, University of Sheffield, Sheffield S10 2TN, UK.
BMC Biol. 2010 Apr 19;8:65. doi: 10.1186/1741-7007-8-65.
In mammalian cells, the integrity of the primary cilium is critical for proper regulation of the Hedgehog (Hh) signal transduction pathway. Whether or not this dependence on the primary cilium is a universal feature of vertebrate Hedgehog signalling has remained contentious due, in part, to the apparent divergence of the intracellular transduction pathway between mammals and teleost fish.
Here, using a functional Gli2-GFP fusion protein, we show that, as in mammals, the Gli2 transcription factor localizes to the primary cilia of cells in the zebrafish embryo and that this localization is modulated by the activity of the Hh pathway. Moreover, we show that the Igu/DZIP1protein, previously implicated in the modulation of Gli activity in zebrafish, also localizes to the primary cilium and is required for its proper formation.
Our findings demonstrate a conserved role of the primary cilium in mediating Hedgehog signalling activity across the vertebrate phylum and validate the use of the zebrafish as a representative model for the in vivo analysis of vertebrate Hedgehog signalling.
在哺乳动物细胞中，初级纤毛的完整性对于 Hedgehog（Hh）信号转导途径的正常调节至关重要。初级纤毛对脊椎动物 Hedgehog 信号传导的依赖性是否是普遍特征，部分原因是哺乳动物和硬骨鱼之间细胞内转导途径的明显分歧。
在这里，我们使用功能性 Gli2-GFP 融合蛋白表明，与哺乳动物一样，Gli2 转录因子定位于斑马鱼胚胎中细胞的初级纤毛，并且这种定位受 Hh 途径活性的调节。此外，我们还表明，先前在斑马鱼中涉及 Gli 活性调节的 Igu/DZIP1 蛋白也定位于初级纤毛，并且对于其正常形成是必需的。
我们的研究结果表明，初级纤毛在跨脊椎动物门介导 Hedgehog 信号活性方面发挥着保守作用，并验证了使用斑马鱼作为体内分析脊椎动物 Hedgehog 信号的代表性模型。
