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Modelling cell cycle synchronisation in networks of coupled radial glial cells

Barrack, Duncan; Thul, Ruediger; Owen, Markus R.

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Authors

Duncan Barrack



Abstract

Radial glial cells play a crucial role in the embryonic mammalian brain. Their proliferation is thought to be controlled, in part, by ATP mediated calcium signals. It has been hypothesised that these signals act to locally synchronise cell cycles, so that clusters of cells proliferate together, shedding daughter cells in uniform sheets. In this paper we investigate this cell cycle synchronisation by taking an ordinary differential equation model that couples the dynamics of intracellular calcium and the cell cycle and extend it to populations of cells coupled via extracellular ATP signals. Through bifurcation analysis we show that although ATP mediated calcium release can lead to cell cycle synchronisation, a number of other asynchronous oscillatory solutions including torus solutions dominate the parameter space and cell cycle synchronisation is far from guaranteed. Despite this, numerical results indicate that the transient and not the asymptotic behaviour of the system is important in accounting for cell cycle synchronisation. In particular, quiescent cells can be entrained on to the cell cycle via ATP mediated calcium signals initiated by a driving cell and crucially will cycle in near synchrony with the driving cell for the duration of neurogenesis. This behaviour is highly sensitive to the timing of ATP release, with release at the G1/S phase transition of the cell cycle far more likely to lead to near synchrony than release during mid G1 phase. This result, which suggests that ATP release timing is critical to radial glia cell cycle synchronisation may help to understand normal and pathological brain development.

Citation

Barrack, D., Thul, R., & Owen, M. R. (2015). Modelling cell cycle synchronisation in networks of coupled radial glial cells. Journal of Theoretical Biology, 377, https://doi.org/10.1016/j.jtbi.2015.04.013

Journal Article Type Article
Acceptance Date Apr 8, 2015
Publication Date Apr 20, 2015
Deposit Date May 24, 2016
Publicly Available Date May 24, 2016
Journal Journal of Theoretical Biology
Print ISSN 0022-5193
Electronic ISSN 1095-8541
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 377
DOI https://doi.org/10.1016/j.jtbi.2015.04.013
Keywords Cell Cycle, Calcium Dynamics, Radial Glial Cells, Cell Cycle Synchronisation, Bifurcation Analysis
Public URL https://nottingham-repository.worktribe.com/output/749397
Publisher URL http://www.sciencedirect.com/science/article/pii/S0022519315001757
Contract Date May 24, 2016

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