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Modelling the coupling between intracellular calcium release and the cell cycle during cortical brain development

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

Authors

Duncan Barrack

MARKUS OWEN markus.owen@nottingham.ac.uk
Professor of Mathematical Biology



Abstract

Most neocortical neurons formed during embryonic brain development arise from radial glial cells which communicate, in part, via ATP mediated calcium signals. Although the intercellular signalling mechanisms that regulate radial glia proliferation are not well understood, it has recently been demonstrated that ATP dependent intracellular calcium release leads to an increase of nearly 100% in overall cellular proliferation. It has been hypothesised that cytoplasmic calcium accelerates entry into S phase of the cell cycle and/or acts to recruit otherwise quiescent cells onto the cell cycle. In this paper we study this cell cycle acceleration and recruitment by forming a differential equation model for ATP mediated calcium-cell cycle coupling via Cyclin D in a single radial glial cell.
Bifurcation analysis and numerical simulations suggest that the cell cycle period depends only weakly on cytoplasmic calcium. Therefore the accelerative impact of calcium on the cell cycle can only account for a small fraction of the large increase in proliferation observed experimentally. Crucially however, our bifurcation analysis reveals that stable fixed point and stable limit cycle solutions can coexist, and that calcium dependent Cyclin D dynamics extend the oscillatory region to lower Cyclin D synthesis rates, thus rendering cells more susceptible to cycling. This supports the hypothesis that cycling glial cells recruit quiescent cells (in G0 phase) onto the cell cycle, via a calcium signalling mechanism, and that this may be the primary means by which calcium augments proliferation rates at the population scale. Numerical simulations of two coupled cells demonstrate that such a scenario is indeed feasible

Journal Article Type Article
Publication Date Apr 21, 2014
Journal Journal of Theoretical Biology
Print ISSN 0022-5193
Electronic ISSN 1095-8541
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 347
APA6 Citation Barrack, D., Thul, R., & Owen, M. R. (2014). Modelling the coupling between intracellular calcium release and the cell cycle during cortical brain development. Journal of Theoretical Biology, 347, https://doi.org/10.1016/j.jtbi.2014.01.004
DOI https://doi.org/10.1016/j.jtbi.2014.01.004
Keywords Cell Cycle, Calcium Dynamics, Radial Glial Cells, Bifurcation Analysis
Publisher URL http://www.sciencedirect.com/science/article/pii/S0022519314000137
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





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