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首页> 外文期刊>Molecular and Cellular Biology >Characterization of NF-κΒ/IκΒ Proteins in Zebra Fish and Their Involvement in Notochord Development
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Characterization of NF-κΒ/IκΒ Proteins in Zebra Fish and Their Involvement in Notochord Development

机译：斑马鱼中NF-κΒ/IκΒ蛋白的表征及其在脊索动物发育中的作用

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Although largely involved in innate and adaptive immunity, NF-κB plays an important role in vertebrate development. In chicks, the inactivation of the NF-κΒ pathway induces functional alterations of the apical ectodermal ridge, which mediates limb outgrowth. In mice, the complete absence of NF-κB activity leads to prenatal death and neural tube defects. Here, we report the cloning and characterization of NF-κΒ/IκB proteins in zebra fish. Despite being ubiquitously expressed among the embryonic tissues, NF-κΒ/IκB members present distinct patterns of gene expression during the early zebra fish development. Biochemical assays indicate that zebra fish NF-κΒ proteins are able to bind consensus DNA-binding (κB) sites and inhibitory IκBα proteins from mammals. We show that zebra fish IκBαs are degraded in a time-dependent manner after induction of transduced murine embryo fibroblasts (MEFs) and that these proteins are able to rescue NF-κΒ activity in IκBα?/? MEFs. Expression of a dominant-negative form of the murine IκBα (mIκBαM), which is able to block NF-κΒ in zebra fish cells, interferes with the notochord differentiation, generating no tail (ntl)-like embryos. This phenotype can be rescued by coinjection of the T-box gene ntl (Brachyury homologue), which is typically required for the formation of posterior mesoderm and axial development, suggesting that ntl lies downstream of NF-κΒ. We further show that ntl and Brachyury promoter regions contain functional κB sites and NF-κΒ can directly modulate ntl expression. Our study illustrates the conservation and compatibility of NF-κΒ/IκB proteins among vertebrates and the importance of NF-κΒ pathway in mesoderm formation during early embryogenesis.
机译：尽管NF-κB主要参与先天和适应性免疫，但在脊椎动物发育中起着重要作用。在雏鸡中，NF-κB通路的失活诱导了根尖外胚层functional的功能改变，从而介导了肢体的生长。在小鼠中，完全不存在NF-κB活性会导致产前死亡和神经管缺陷。在这里，我们报告了斑马鱼中NF-κB/IκB蛋白的克隆和鉴定。尽管在胚胎组织中普遍表达，但NF-κB/IκB成员在斑马鱼早期发育过程中呈现出不同的基因表达模式。生化分析表明，斑马鱼的NF-κΒ蛋白能够结合哺乳动物的共有DNA结合（κB）位点和抑制性IκBα蛋白。结果表明，斑马鱼IκBαs在诱导鼠类成纤维细胞（MEFs）诱导后以时间依赖性方式降解，并且这些蛋白能够挽救IκBαα/β MEFs中的NF-κΒ活性。鼠IκBα（mIκBαM）的显性负型表达能够阻断斑马鱼细胞中的NF-κΒ，干扰脊索分化，产生 no tail （ ntl < / em>）的胚胎。这种表型可以通过共同注射T-box基因 ntl （ Brachyury 同源物）来挽救，这通常是后中胚层形成和轴向发育所必需的，提示< em> ntl 位于NF-κΒ的下游。我们进一步表明 ntl 和 Brachyury 启动子区域含有功能性κB位点，NF-κΒ可以直接调节 ntl 的表达。我们的研究说明了脊椎动物中NF-κB/IκB蛋白的保守性和相容性，以及早期胚胎发生过程中中胚层形成中NF-κB通路的重要性。

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