Convergence of Wnt and FGF signals in the genesis of posterior neural plate through activation of the Sox2 enhancer N-1
Convergence of Wnt and FGF signals in the genesis of posterior neural plate through activation of the Sox2 enhancer N-1
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DOI：
10.1242/dev.02196
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发表时间：
2006-01-01
期刊：
影响因子：
4.6
通讯作者：
Kondoh, H
中科院分区：
文献类型：
--
作者：
Takemoto, T;Uchikawa, M;Kondoh, H
转录因子基因Sox 2的表达精确地标记了各种脊椎动物物种的神经板。我们以前表明，Sox 2的表达占主导地位的鸡胚的神经板实际上是由五个具有离散区域覆盖，其中420 bp长的增强子N-1，活跃在节点近端区域，可能是直接参与后神经板的发生协调遗传上保守的增强子。我们研究了调节这种增强子的信号系统，首先确定了56 bp的N-1核心增强子（N-1c），它以三聚体形式重现了增强子N-1的活性。突变分析确定了五个区块，A到E，调节增强子N-1c。这些块的功能分析表明，Writ和FGF信号协同激活增强子，通过块A-B，结合Lef 1，和块D，分别。Fgf 8b和Wnt 8 c在组织器原条区表达，解释了胚胎中的活性。阻断E对于抑制中内胚层前体中的增强子N-Ic活性是必需的。增强子N-1c不受BMP信号的影响。因此，Wnt和FGF信号会聚以通过增强子N-lc激活Sox 2表达，揭示Writ信号直接参与神经板发育的起始。
The expression of the transcription factor gene Sox2 precisely marks the neural plate in various vertebrate species. We previously showed that the Sox2 expression prevailing in the neural plate of chicken embryos is actually regulated by the coordination of five phylogenetically conserved enhancers having discrete regional coverage, among which the 420-bp long enhancer N-1, active in the node-proximal region, is probably involved directly in the genesis of the posterior neural plate. We investigated the signaling systems regulating this enhancer, first identifying the 56-bp N-1 core enhancer (N-1c), which in a trimeric form recapitulates the activity of the enhancer N-1. Mutational analysis identified five blocks, A to E, that regulate the enhancer N-1c. Functional analysis of these blocks indicated that Writ and FGF signals synergistically activate the enhancer through Blocks A-B, bound by Lef1, and Block D, respectively. Fgf8b and Wnt8c expressed in the organizer-primitive streak region account for the activity in the embryo. Block E is essential for the repression of the enhancer N-1 c activity in the mesendodermal precursors. The enhancer N-1c is not affected by BMP signals. Thus, Wnt and FGF signals converge to activate Sox2 expression through the enhancer N-1 c, revealing the direct involvement of the Writ signal in the initiation of neural plate development.