Regulation of dorsal gene expression in Xenopus by the ventralizing homeodomain gene Vox.
Regulation of dorsal gene expression in Xenopus by the ventralizing homeodomain gene Vox.
复制标题
腹侧同源域基因 Vox 对非洲爪蟾背侧基因表达的调节。
DOI：
10.1006/dbio.1999.9296
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发表时间：
1999
影响因子：
2.7
通讯作者：
Kimelman,D
中科院分区：
文献类型：
--
作者：
Melby,AE;Clements,WK;Kimelman,D
脊椎动物胚胎中的图案化是由来自背侧组织者和腹侧表达的BMP的信号之间的相互作用控制的。在这里，我们研究Vox的功能，Vox是一个含有同源结构域的基因，由腹侧信号BMP-4激活。使用显性负性BMP受体（ΔBMPR）抑制BMP信号传导导致腹侧边缘区中背侧基因的异位激活，并且这种激活通过共注射Vox来阻止。脊索蛋白是由ΔBMPR上调的那些基因中最强烈激活的，并且是由Vox表达最强烈抑制的基因。我们证明，Vox作为一个转录抑制因子，显示本地Vox的活性是模仿的Vox-抑制融合（VoxEnR）和一个Vox激活融合（VoxG 4A）作为一个反形，导致形成的部分二级轴时，在胚胎的腹侧表达。尽管Vox可以异位激活整个胚胎中的BMP-4表达，但我们没有看到VoxG 4A激活BMP-4，表明这种激活是间接的。使用VoxG 4A的胚胎诱导型版本，我们发现Vox功能的关键时间窗口是在囊胚晚期。使用这个构建体，我们证明，只有一个子集的背基因是直接抑制Vox，揭示了组织者基因有不同的调控模式。由于Vox抑制的主要直接靶点是脊索蛋白，我们建议Vox通过限制脊索蛋白的表达结构域来建立BMP-4形态发生梯度。
Patterning in the vertebrate embryo is controlled by an interplay between signals from the dorsal organizer and the ventrally expressed BMPs. Here we examine the function of Vox, a homeodomain-containing gene that is activated by the ventralizing signal BMP-4. Inhibition of BMP signaling using a dominant negative BMP receptor (ΔBMPR) leads to the ectopic activation of dorsal genes in the ventral marginal zone, and this activation is prevented by co-injection of Vox. chordin is the most strongly activated of those genes that are up-regulated by ΔBMPR and is the gene most strongly inhibited by Vox expression. We demonstrate that Vox acts as a transcriptional repressor, showing that the activity of native Vox is mimicked by a Vox-repressor fusion (VoxEnR) and that a Vox-activator fusion (VoxG4A) acts as an antimorph, causing the formation of a partial secondary axis when expressed on the ventral side of the embryo. Although Vox can ectopically activate BMP-4 expression in whole embryos, we see no activation of BMP-4 by VoxG4A, demonstrating that this activation is indirect. Using a hormone-inducible version of VoxG4A, we find that a critical time window for Vox function is during the late blastula period. Using this construct, we demonstrate that only a subset of dorsal genes is directly repressed by Vox, revealing that there are different modes of regulation for organizer genes. Since the major direct target for Vox repression is chordin, we propose that Vox acts in establishing a BMP-4 morphogen gradient by restricting the expression domain of chordin.