A mathematical model of the biochemical network underlying left-right asymmetry establishment in mammals
Date
2018
Authors
Roussel, Catharine J.
Roussel, Marc R.
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
The expression of the TGF-β protein Nodal on the left side of vertebrate embryos is a determining event in the development of internal-organ asymmetry. We present a mathematical model for the control of the expression of Nodal and its antagonist Lefty consisting entirely of realistic elementary reactions. We analyze the model in the absence of Lefty and find a wide range of parameters over which bistability (two stable steady states) is observed, with one stable steady state a low-Nodal state corresponding to the right-hand developmental fate, and the other a high-Nodal state corresponding to the left. We find that bistability requires a transcription factor containing two molecules of phosphorylated Smad2. A numerical survey of the full model, including Lefty, shows the effects of Lefty on the potential for bistability, and on the conditions that lead to the system reaching one or the other steady state.
Description
Accepted author manuscript.
Keywords
Development , Asymmetry , Mouse , Nodal , Lefty , Mathematical model , Biochemical network
Citation
Roussel, C. J., & Roussel, M. R. (2018). A mathematical model of the biochemical network underlying left-right asymmetry establishment in mammals. BioSystems, 173, 281-297. doi:10.1016/j.biosystems.2018.10.003