Abstract
BackgroundSomitogenesis is a fundamental characteristic feature of development in various animal embryos. Molecular evidence has proved that the Notch and Wnt pathways play important roles in regulating the process of somitogenesis and there is crosstalk between these two pathways. However, it is difficult to investigate the detailed mechanism of these two pathways and their interactions in somitogenesis through biological experiments. In recent years some mathematical models have been proposed for the purpose of studying the dynamics of the Notch and Wnt pathways in somitogenesis. Unfortunately, only a few of these models have explored the interactions between them.ResultsIn this study, we have proposed three mathematical models for the Notch signalling pathway alone, the Wnt signalling pathway alone, and the interactions between them. These models can simulate the dynamics of the Notch and Wnt pathways in somitogenesis, and are capable of reproducing the observations derived from wet experiments. They were used to investigate the molecular mechanisms of the Notch and Wnt pathways and their crosstalk in somitogenesis through the model simulations.ConclusionsThree mathematical models are proposed for the Notch and Wnt pathways and their interaction during somitogenesis. The simulations demonstrate that the extracellular Notch and Wnt signals are essential for the oscillating expressions of both Notch and Wnt target genes. Moreover, the internal negative feedback loops and the three levels of crosstalk between these pathways play important but distinct roles in maintaining the system oscillation. In addition, the results of the parameter sensitivity analysis of the models indicate that the Notch pathway is more sensitive to perturbation in somitogenesis.
Highlights
Somitogenesis is a fundamental characteristic feature of development in various animal embryos
The simulations demonstrate that the extracellular Notch and Wnt signals are essential for the oscillating expressions of both Notch and Wnt target genes
The results of the parameter sensitivity analysis of the models indicate that the Notch pathway is more sensitive to perturbation in somitogenesis
Summary
Somitogenesis is a fundamental characteristic feature of development in various animal embryos. The Notch and Wnt pathways regulate the oscillating expressions of their target genes, which play major roles in controlling somite formation [4,5,6]. In 2003 Julian Lewis et al proposed a simple mathematical model of the Notch pathway in zebrafish somitogenesis [7] They modeled the oscillating expressions of Notch pathway target genes by introducing two feedback loops. In 2007, J.G. Rodríguez-González et al proposed a mathematical model to investigate the interaction between the Notch and the Wnt pathways in the segmentation clock in mice [11]. Kazama et al proposed a mathematical model to reveal the interaction of the Notch and Wnt pathways in the segmentation clock [14]. More accurate and complicated mathematical models are still needed to further our understanding of the detailed mechanism of the Notch and Wnt pathways and their crosstalk in somitogenesis
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