GapNet - combining mathematical modelling & experiment to explore the role of gap junctions in Xenopus development

Steve Baigent and Anne Warner

Cells in early embryos are interconnected by gap junctions which allow small molecules, including many that are intracellular signalling molecules, to be transferred directly between cells. Gap junctions provide a pathway that could transfer signals that direct development. Therefore an understanding of the properties of gap junctions and how they change as development proceeds is of considerable importance.

In living embryos gap junction behaviour can be explored by injecting small fluorescent dyes into one cell and observing the pattern of dye spread. Experiments show that in the 32 cell amphibian embryo cells in future dorsal regions exchange small molecules with their neighbours more frequently and more efficiently than cells in future ventral regions. This suggests that the properties of gap junctions are not uniform across a given embryo. We (N. Mulrine, A. Miller, J.Hall & A.Warner) subsequently analysed the electrical properties of gap junctions between isolated pairs of embryonic cells and found complex time and voltage dependent properties.

Multiple paths for current flow between cells in intact, multicellular embryos make quantitative analysis of the properties of gap junctions between individual cells very difficult. To investigate how the properties of individual gap junctions might contribute to behaviour in the intact embryo, we (S. Baigent, J. Stark & A. Warner) first constructed a mathematical model of a pair of cells connected by a single gap junction and set out to reproduce the experimental behaviour. Our analysis revealed new information, not easily obtained experimentally, about the potential for hysteresis. We are now constructing network models of multicellular embryos (`GapNet') in order to explore how individual gap junction properties might influence behaviour of whole embryos.

We shall present examples of properties of gap junctions in early amphibian embryos determined experimentally, show how the 2-cell model matches experiment and report on progress with the mathematical analysis of multicellular systems.

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