Kzp controls canonical wnt8 signaling to modulate dorsoventral patterning during zebrafish gastrulation.
Kzp controls canonical wnt8 signaling to modulate dorsoventral patterning during zebrafish gastrulation.
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DOI：
10.1074/jbc.a110.161554
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发表时间：
2012-10
期刊：
影响因子：
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通讯作者：
Shaohua Yao;Meilin Qian;Senyi Deng;Lifang Xie;Han-Suo Yang;Chun Xiao;Ting Zhang;Hong Xu;Xia Z
中科院分区：
文献类型：
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作者：
Shaohua Yao;Meilin Qian;Senyi Deng;Lifang Xie;Han-Suo Yang;Chun Xiao;Ting Zhang;Hong Xu;Xia Z
在脊椎动物胚胎发育过程中，体轴的形成需要Wnt信号及其拮抗剂的作用。合子典型wnt 8表达仅出现在腹外侧边缘，并介导Wnt/β-连环蛋白活性以促进后部和腹侧细胞命运。然而，合子wnt 8信号启动的机制知之甚少。在这里，我们确定了一种新的，母系衍生的转录因子，Kzp（Kaiso锌指蛋白），作为一个重要的决定因素，在斑马鱼合子Wnt信号的启动。Kzp是一种DNA结合转录因子，通过锌指识别特定的共有DNA序列5 '-（t/a/g）t（a/t/g）nctgcca-3'，并通过直接结合wnt 8启动子来控制斑马鱼胚胎发育过程中合子wnt 8表达的起始。消耗Kzp强烈背化胚胎，其特征在于背基因表达的扩展。Kzp的过表达引起后验化。这些表型与wnt 8缺失或过表达诱导的表型高度相似，并通过改变wnt 8活性而获救。因此，我们的研究结果提供了第一个深入了解的机制，参与启动合子典型的Wnt信号的母源性转录因子。
During vertebrate embryonic development, the body axis formation requires the action of Wnt signals and their antagonists. Zygotic canonical wnt8 expression appears exclusively at the ventrolateral margin and mediates Wnt/β-catenin activities to promote posterior and ventral cell fate. However, the mechanisms involved in the initiation of zygotic wnt8 signals are poorly understood. Here, we identify a novel, maternally derived transcription factor, Kzp (Kaiso zinc finger-containing protein), as an important determinant for the initiation of zygotic Wnt signals in zebrafish. Kzp is a DNA-binding transcription factor that recognizes specific consensus DNA sequences, 5'-(t/a/g)t(a/t/g)nctgcca-3', through zinc fingers and controls the initiation of zygotic wnt8 expression by directly binding to the wnt8 promoter during zebrafish embryonic development. Depletion of Kzp strongly dorsalized embryos, which was characterized by the expansion of dorsal gene expression. Overexpression of Kzp caused posteriorization. These phenotypes were highly similar to ones induced by wnt8 depletion or overexpression and were rescued by alteration of wnt8 activity. Thus, our results provide the first insight into the mechanism involved in the initiation of zygotic canonical Wnt signals by a maternally derived transcription factor.