Modelling coupled oscillations in the Notch, Wnt, and FGF signaling pathways during somitogenesis: a comprehensive mathematical model.

Hong-Yan Wang,Zhi-Qiang Ma,Ying Sun,Lu-Guo Sun,Li-Hua Zheng,Yu-Xin Li,Yin Wu,Chun-Lei Yu,Zhen-Bo Song,Yan-Xin Huang,Guan-Nan Wang,Yong-Li Bao

doi:10.1155/2015/387409

Abstract

Somite formation in the early stage of vertebrate embryonic development is controlled by a complicated gene network named segmentation clock, which is defined by the periodic expression of genes related to the Notch, Wnt, and the fibroblast growth factor (FGF) pathways. Although in recent years some findings about crosstalk among the Notch, Wnt, and FGF pathways in somitogenesis have been reported, the investigation of their crosstalk mechanisms from a systematic point of view is still lacking. In this study, a more comprehensive mathematical model was proposed to simulate the dynamics of the Notch, Wnt, and FGF pathways in the segmentation clock. Simulations and bifurcation analyses of this model suggested that the concentration gradients of both Wnt, and FGF signals along the presomitic mesoderm (PSM) are corresponding to the whole process from start to stop of the segmentation clock. A number of highly sensitive parameters to the segmentation clock's oscillatory pattern were identified. By further bifurcation analyses for these sensitive parameters, and several complementary mechanisms in respect of the maintenance of the stable oscillation of the segmentation clock were revealed.

Highlights

In the early stage of vertebrate embryonic development, the body is organized in a series of functionally equivalent units, each comprising a vertebra, its associated muscles, peripheral nerves, and blood vessels called somite [1]
The simulation results indicate that the regulation of the Wnt pathway to the Notch pathway through Mesogenin 1 (Msgn1) is essential to the stable oscillations of Notch target genes
When the Wnt or fibroblast growth factor (FGF) signal is in the closed range target genes are not expressed. These results show that the concentration gradients of both Wnt and FGF signals along the presomitic mesoderm (PSM) are corresponding to the whole process from start to stop of the segmentation clock

Summary

Introduction

In the early stage of vertebrate embryonic development, the body is organized in a series of functionally equivalent units, each comprising a vertebra, its associated muscles, peripheral nerves, and blood vessels called somite [1]. For nearly a decade it has been known that the Notch pathway, the Wnt pathway, and the FGF pathway are the major components of the segmentation clock [3]. These pathways regulate the oscillatory expressions of their target genes, which play major roles in controlling somite formation [4,5,6]. The first mathematical model of the Notch pathway was developed by Lewis [7] They modelled a simple oscillation of Her1/7 gene expression in the embryo of zebrafish by introducing a negative feedback loop formed by the inhibition of Her1/7 protein to the transcription of itself. From previous two models, a more complex model for the Notch pathway was proposed by Agrawal et al to investigate cell

Methods

Results

Conclusion