Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development
Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development
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DOI：
10.1038/msb.2010.9
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发表时间：
2010-03-01
影响因子：
9.9
通讯作者：
Driever, Wolfgang
中科院分区：
文献类型：
--
作者：
Onichtchouk, Daria;Geier, Florian;Driever, Wolfgang
转录因子POU 5 f1/OCT 4控制哺乳动物ES细胞的多能性，但对其在早期胚胎中的功能知之甚少。我们使用时间分辨转录组分析斑马鱼pou 5 f1 MZspg突变胚胎，以确定Pou 5 f1调控的基因。比较哺乳动物系统定义进化保守的Pou 5 f1目标。时间序列数据揭示了许多Pou 5 f1靶点具有延迟或提前的表达起始。我们确定了两个Pou 5 f1依赖的机制控制发育的时间。首先，几个Pou 5 f1的目标是转录抑制因子，介导不同的胚胎隔室分化基因的抑制。我们分析her 3基因调控作为神经原基中阻遏物的例子。其次，SoxB 1组基因表达和Pou 5 f1依赖性调节her 3和foxD 3的动力学揭示了SoxB 1活性的差异要求，以控制激活的时间动力学和胚胎中靶点的空间分布。我们建立了早期Pou 5 f1和SoxB 1基因网络的数学模型，以展示对发育时序重要的调控特征。斑马鱼Pou 5 f1靶网络的时空结构可以解释哺乳动物干细胞网络进化的各个方面。Molecular Systems Biology 6：354; 2010年3月9日在线发表; doi：10.1038/msb.2010.9
The transcription factor POU5f1/OCT4 controls pluripotency in mammalian ES cells, but little is known about its functions in the early embryo. We used time-resolved transcriptome analysis of zebrafish pou5f1 MZspg mutant embryos to identify genes regulated by Pou5f1. Comparison to mammalian systems defines evolutionary conserved Pou5f1 targets. Time-series data reveal many Pou5f1 targets with delayed or advanced onset of expression. We identify two Pou5f1-dependent mechanisms controlling developmental timing. First, several Pou5f1 targets are transcriptional repressors, mediating repression of differentiation genes in distinct embryonic compartments. We analyze her3 gene regulation as example for a repressor in the neural anlagen. Second, the dynamics of SoxB1 group gene expression and Pou5f1-dependent regulation of her3 and foxD3 uncovers differential requirements for SoxB1 activity to control temporal dynamics of activation, and spatial distribution of targets in the embryo. We establish a mathematical model of the early Pou5f1 and SoxB1 gene network to demonstrate regulatory characteristics important for developmental timing. The temporospatial structure of the zebrafish Pou5f1 target networks may explain aspects of the evolution of the mammalian stem cell networks. Molecular Systems Biology 6: 354; published online 9 March 2010; doi: 10.1038/msb.2010.9