Tiedemann Hendrik B, Schneltzer Elida, Zeiser Stefan, Rubio-Aliaga Isabel, Wurst Wolfgang, Beckers Johannes, Przemeck Gerhard K H, Hrabé de Angelis Martin
Institute of Experimental Genetics, GSF-National Research Centre for Environment and Health, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany.
J Theor Biol. 2007 Sep 7;248(1):120-9. doi: 10.1016/j.jtbi.2007.05.014. Epub 2007 May 21.
To model dynamic expression patterns in somitogenesis we developed a Java-application for simulating gene regulatory networks in many cells in parallel and visualising the results using the Java3D API, thus simulating the collective behaviour of many thousand cells. According to the 'clock-and-wave-front' model mesodermal segmentation of vertebrate embryos is regulated by a 'segmentation clock', which oscillates with a period of about 2h in mice, and a 'wave front' moving back with the growing caudal end of the presomitic mesoderm. The clock is realised through cycling expression of genes such as Hes1 and Hes7, whose gene products repress the transcription of their encoding genes in a negative feedback loop. By coupling the decay of the Hes1 mRNA to a gradient with the same features and mechanism of formation as the mesodermal Fgf8 gradient we can simulate typical features of the dynamic expression pattern of Hes1 in the presomitic mesoderm. Furthermore, our program is able to synchronise Hes1 oscillations in thousands of cells through simulated Delta-Notch signalling interactions.
为了模拟体节发生过程中的动态表达模式，我们开发了一个Java应用程序，用于并行模拟许多细胞中的基因调控网络，并使用Java3D API可视化结果，从而模拟数千个细胞的集体行为。根据“时钟和波前”模型，脊椎动物胚胎的中胚层分割由一个“分割时钟”调节，该时钟在小鼠中以约2小时的周期振荡，以及一个随着前体节中胚层尾端的生长而后退的“波前”。时钟是通过Hes1和Hes7等基因的循环表达实现的，其基因产物在负反馈回路中抑制其编码基因的转录。通过将Hes1 mRNA的衰减与具有与中胚层Fgf8梯度相同特征和形成机制的梯度耦合，我们可以模拟前体节中胚层中Hes Hes1动态表达模式的典型特征。此外，我们的程序能够通过模拟Delta-Notch信号相互作用，使数千个细胞中的Hes1振荡同步。
