Bistability in a model of mesoderm and anterior mesendoderm specification in Xenopus laevis.

ABSTRACT

In this paper we develop a model of mesendoderm specification in Xenopus laevis based on an existing gene regulation network. The mesendoderm is a population of cells that may contribute to either the mesoderm or endoderm. The model that we develop encompasses the time evolution of transcription factor concentrations in a single cell and is shown to have stable steady states that correspond to mesoderm and anterior mesendodermal cell types, but not endoderm (except in cells where Goosecoid expression is inhibited). Both in vitro and in vivo versions of the model are developed and analysed, the former indicating how cell fate is determined in large part by the concentration of Activin administered to a cell, with the model results comparing favourably with current quantitative experimental data. A numerical investigation of the in vivo model suggests that cell fate is determined largely by a VegT and beta-Catenin pre-pattern, subsequently being reinforced by Nodal. We argue that this sensitivity of the model to a VegT and beta-Catenin pre-pattern indicates that a key VegT self-limiting mechanism (for which there is experimental evidence) is absent from the model. Furthermore, we find that the lack of a steady state corresponding to endoderm is entirely consistent with current in vivo data, and that the in vivo model corresponds to mesendoderm specification on the dorsal, but not the ventral, side of the embryo.