Unexpected functional redundancy between Twist and Slug (Snail2) and their feedback regulation of NF-kappaB via Nodal and Cerberus.
Unexpected functional redundancy between Twist and Slug (Snail2) and their feedback regulation of NF-kappaB via Nodal and Cerberus.
复制标题
Twist 和 Slug (Snail2) 之间意外的功能冗余以及它们通过 Nodal 和 Cerberus 对 NF-kappaB 的反馈调节。
DOI：
10.1016/j.ydbio.2009.04.016
复制
发表时间：
2009
影响因子：
2.7
通讯作者：
Klymkowsky,MichaelW
中科院分区：
文献类型：
--
作者：
Zhang,Chi;Klymkowsky,MichaelW
一个NF-κB-Twist-Snail网络控制果蝇轴和中胚层的形成。利用翻译阻断morpholinos和激素调节蛋白，我们证明了早期非洲爪蟾胚胎中类似网络的存在。twist （twist1）功能的丧失导致中胚层和神经嵴标记物减少，细胞凋亡增加，snail1（蜗牛）和snail2（蛞蝓）mRNA水平下降。注射snail2 mRNA可以挽救twist的功能表型损失，反之亦然。在胚胎早期，NF-κB/RelA调控twist、snail2和snail1 mRNA水平；类似地，Nodal/Smad2调节twist、snail2、snail1和relA RNA水平。Twist和Snail2都能负向调节cerberus RNA的水平，cerberus RNA编码结、骨形态发生蛋白（BMP）和Wnt抑制剂。Cerberus抗nodal活性抑制NF-κB活性，降低relA RNA水平。这些结果揭示了脊椎动物中胚层规范网络核心的保守和意想不到的调节相互作用。
A NF-κB-Twist-Snail network controls axis and mesoderm formation in Drosophila. Using translation-blocking morpholinos and hormone-regulated proteins, we demonstrate the presence of an analogous network in the early Xenopus embryo. Loss of twist (twist1) function leads to a reduction of mesoderm and neural crest markers, an increase in apoptosis, and a decrease in snail1 (snail) and snail2 (slug) mRNA levels. Injection of snail2 mRNA rescues twist's loss of function phenotypes and visa versa. In the early embryo NF-κB/RelA regulates twist, snail2, and snail1 mRNA levels; similarly Nodal/Smad2 regulate twist, snail2, snail1, and relA RNA levels. Both Twist and Snail2 negatively regulate levels of cerberus RNA, which encodes a Nodal, bone morphogenic protein (BMP), and Wnt inhibitor. Cerberus's anti-Nodal activity inhibits NF-κB activity and decreases relA RNA levels. These results reveal both conserved and unexpected regulatory interactions at the core of a vertebrate's mesodermal specification network.