Cotterell James, Robert-Moreno Alexandre, Sharpe James
EMBL-CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), Barcelona 08002, Spain.
EMBL-CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), Barcelona 08002, Spain.
Cell Syst. 2015 Oct 28;1(4):257-69. doi: 10.1016/j.cels.2015.10.002.
During somitogenesis in embryos, a posteriorly moving differentiation front arrests the oscillations of "segmentation clock" genes, leaving behind a frozen, periodic pattern of expression stripes. Both mathematical theories and experimental observations have invoked a "clock and wavefront" model to explain this phenomenon, in which long-range molecular gradients control the movement of the front and therefore the placement of the stripes in the embryo. Here, we develop a fundamentally different model-a progressive oscillatory reaction-diffusion (PORD) system driven by short-range interactions. In this model, posterior movement of the front is a local, emergent phenomenon that, in contrast to the clock and wavefront model, is not controlled by global positional information. The PORD model explains important features of somitogenesis, such as size regulation, that previous reaction-diffusion models could not explain. Moreover, the PORD and clock and wavefront models make different predictions about the results of FGF-inhibition and tissue-cutting experiments, and we demonstrate that the results of these experiments favor the PORD model.
在胚胎体节发生过程中,一个向后移动的分化前沿会使“体节时钟”基因的振荡停止,从而留下一种冻结的、周期性的表达条纹模式。数学理论和实验观察都援引了“时钟和波前”模型来解释这一现象,在该模型中,长程分子梯度控制着前沿的移动,进而控制着条纹在胚胎中的位置。在此,我们开发了一个根本不同的模型——由短程相互作用驱动的渐进振荡反应扩散(PORD)系统。在这个模型中,前沿的向后移动是一种局部的、涌现的现象,与时钟和波前模型不同,它不受全局位置信息的控制。PORD模型解释了体节发生的重要特征,如大小调控,而之前的反应扩散模型无法解释这些特征。此外,PORD模型和时钟与波前模型对成纤维细胞生长因子(FGF)抑制和组织切割实验的结果做出了不同的预测,我们证明这些实验的结果支持PORD模型。