Multicellular Mathematical Modelling of Mesendoderm Formation in Amphibians

The earliest cell fate decisions in a developing embryo are those associated with establishing the germ layers. The specification of the mesoderm and endoderm is of particular interest as the mesoderm is induced from the endoderm, potentially from an underlying bipotential group of cells, the mesendoderm. Mesendoderm formation has been well studied in an amphibian model frog, Xenopus laevis, and its formation is driven by a gene regulatory network (GRN) induced by maternal factors deposited in the egg. We have recently demonstrated that the axolotl, a urodele amphibian, utilises a different topology in its GRN to specify the mesendoderm. In this paper, we develop spatially structured mathematical models of the GRNs governing mesendoderm formation in a line of cells. We explore several versions of the model of mesendoderm formation in both Xenopus and the axolotl, incorporating the key differences between these two systems. Model simulations are able to reproduce known experimental data, such as Nodal expression domains in Xenopus, and also make predictions about how the positional information derived from maternal factors may be interpreted to drive cell fate decisions. We find that whilst cell-cell signalling plays a minor role in Xenopus, it is crucial for correct patterning domains in axolotl.