Role of Rel/NF-κB transcription factors during the outgrowth of the vertebrate limb
Role of Rel/NF-κB transcription factors during the outgrowth of the vertebrate limb
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DOI：
10.1038/33429
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发表时间：
1998-04-09
期刊：
影响因子：
64.8
通讯作者：
Verma, IM
中科院分区：
文献类型：
--
作者：
Kanegae, Y;Tavares, AT;Verma, IM
脊椎动物肢体的发育是研究导致组织图案化和增殖的信号通路的一个顺从系统（1）。肢起源于特定轴向水平的侧板中胚层细胞的差异生长（2）。在肢原基的尖端，进展区，一组增殖的间充质细胞，诱导上覆的外胚层分化成一个专门的结构，称为顶端外胚层脊。随后的肢体生长需要脊和进展区之间的相互信号传递（3-6）。转录因子的Rel/NF-κ B家族响应于导致细胞生长、分化、炎症反应、凋亡和肿瘤转化的几种信号而被诱导（7）。在未刺激的细胞中，NF-κ B在细胞质中与抑制性蛋白I-κ B相关。响应于外部信号，I-κ B被磷酸化、泛素化和降解，释放NF-κ B进入细胞核并激活转录（7）。在这里，我们表明，Rel/NF-κ B基因表达的进展区的发展鸡肢芽。当Rel/NF-κ B蛋白的活性被产生反显性负I-κ B α蛋白的病毒载体感染阻断时，肢体生长被阻止。我们的结果表明，Rel/NF-κ B转录因子在脊椎动物肢体发育中起作用。
The development of the vertebrate limb serves as an amenable system for studying signaling pathways that lead to tissue patterning and proliferation(1). Limbs originate as a consequence of a differential growth of cells from the lateral plate mesoderm at specific axial levels(2). At the tip of the limb primordia the progress zone, a proliferating group of mesenchymal cells, induces the overlying ectoderm to differentiate into a specialized structure termed the apical ectodermal ridge. Subsequent limb outgrowth requires reciprocal signalling between the ridge and the progress zone(3-6). The Rel/NF-kappa B family of transcription factors is induced in response to several signals that lead to cell growth, differentiation, inflammatory responses, apoptosis and neoplastic transformation(7), In unstimulated cells, NF-kappa B is associated in the cytoplasm with an inhibitory protein, I-kappa B. In response to an external signal, I-kappa B is phosphorylated, ubiquitinated and degraded, releasing NF-kappa B to enter the nucleus and activate transcription(7). Here we show that Rel/NF-kappa B genes are expressed in the progress zone of the developing chick limb bud. When the activity of Rel/NF-kappa B proteins is blocked by infection with viral vectors that produce transdominant-negative I-kappa B alpha proteins, limb outgrowth is arrested, Our results indicate that Rel/NF-kappa B transcription factors play a role in vertebrate limb development.