Repressor dimerization in the zebrafish somitogenesis clock
Repressor dimerization in the zebrafish somitogenesis clock
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DOI：
10.1371/journal.pcbi.0030032
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发表时间：
2007-02-01
影响因子：
4.3
通讯作者：
Cinquin, Olivier
中科院分区：
文献类型：
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作者：
Cinquin, Olivier
体节发生时钟的振荡与脊椎动物胚胎分割的基本过程有关，但对它们的产生知之甚少。在斑马鱼中，已经提出Her蛋白抑制其自身mRNA的转录。然而，在其最简单的形式中，该模型与Her蛋白的吗啉代敲低可损害其mRNA表达的事实不相容。简单的自我抑制模型也不能解释基因表达的时空模式，基因表达的波动随着传播而缩小。在这里，我们研究计算所产生的二聚体的可能性之间的转录阻遏物在斑马鱼的体节发生时钟的财富网络。这些网络可以复制敲除表型，并强烈表明存在Her 1-Her 7异源二聚体，迄今未经实验验证。该网络是第一次报道再现斑马鱼体节发生时钟的时空模式;它们揭示了Her13.2的作用，Her13.2是近轴中胚层中体节发生时钟和位置信息之间唯一已知的联系。网络还可以通过操纵FGF信号来解释时钟的扰动。了解时钟振荡和位置信息之间的相互作用是研究分割机制的关键第一步。
The oscillations of the somitogenesis clock are linked to the fundamental process of vertebrate embryo segmentation, yet little is known about their generation. In zebrafish, it has been proposed that Her proteins repress the transcription of their own mRNA. However, in its simplest form, this model is incompatible with the fact that morpholino knockdown of Her proteins can impair expression of their mRNA. Simple self-repression models also do not account for the spatiotemporal pattern of gene expression, with waves of gene expression shrinking as they propagate. Here we study computationally the networks generated by the wealth of dimerization possibilities amongst transcriptional repressors in the zebrafish somitogenesis clock. These networks can reproduce knockdown phenotypes, and strongly suggest the existence of a Her1-Her7 heterodimer, so far untested experimentally. The networks are the first reported to reproduce the spatiotemporal pattern of the zebrafish somitogenesis clock; they shed new light on the role of Her13.2, the only known link between the somitogenesis clock and positional information in the paraxial mesoderm. The networks can also account for perturbations of the clock by manipulation of FGF signaling. Achieving an understanding of the interplay between clock oscillations and positional information is a crucial first step in the investigation of the segmentation mechanism.