title: Multicellular Mathematical Modelling of Mesendoderm Formation in Amphibians.
abstract: 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.
authors.affiliation: MyCIB, School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, LE12 5RD, UK. laura.brown@slcu.cam.ac.uk.|The Sainsbury Laboratory, University of Cambridge, Bateman Street, Cambridge, CB2 1LR, UK. laura.brown@slcu.cam.ac.uk.
authors.forename: L E
authors.initials: LE
authors.lastname: Brown
authors.affiliation: School of Mathematical Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Middleton
authors.affiliation: School of Mathematical Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: King
authors.affiliation: School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
authors.forename: M
authors.initials: M
authors.lastname: Loose
mesh_terms: D000558:Ambystoma mexicanum / Q000196:embryology / Q000235:genetics; D029845:Amphibian Proteins / Q000235:genetics; D000663:Amphibians / Q000196:embryology* / Q000235:genetics; D000818:Animals; D003198:Computer Simulation; D004707:Endoderm / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D055641:Mathematical Concepts; D008648:Mesoderm / Q000196:embryology; D008954:Models, Biological; D055456:Nodal Signaling Ligands / Q000235:genetics; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics
chemical_list: D029845:Amphibian Proteins; D055456:Nodal Signaling Ligands
keywords: Bistability; Endoderm; Gene regulatory network; Maternal factors; Mesoderm; Positional information