Modelling cell cycle synchronisation in networks of coupled radial glial cells

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, shed...

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Main Authors: Barrack, Duncan, Thul, Ruediger, Owen, Markus R.
Format: Article
Published: Elsevier 2015
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Online Access:https://eprints.nottingham.ac.uk/33482/
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author Barrack, Duncan
Thul, Ruediger
Owen, Markus R.
author_facet Barrack, Duncan
Thul, Ruediger
Owen, Markus R.
author_sort Barrack, Duncan
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-334822020-05-04T17:06:20Z https://eprints.nottingham.ac.uk/33482/ Modelling cell cycle synchronisation in networks of coupled radial glial cells Barrack, Duncan Thul, Ruediger Owen, Markus R. 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. Elsevier 2015-04-20 Article PeerReviewed Barrack, Duncan, Thul, Ruediger and Owen, Markus R. (2015) Modelling cell cycle synchronisation in networks of coupled radial glial cells. Journal of Theoretical Biology, 377 . pp. 85-97. ISSN 1095-8541 Cell Cycle Calcium Dynamics Radial Glial Cells Cell Cycle Synchronisation Bifurcation Analysis http://www.sciencedirect.com/science/article/pii/S0022519315001757 doi:10.1016/j.jtbi.2015.04.013 doi:10.1016/j.jtbi.2015.04.013
spellingShingle Cell Cycle
Calcium Dynamics
Radial Glial Cells
Cell Cycle Synchronisation
Bifurcation Analysis
Barrack, Duncan
Thul, Ruediger
Owen, Markus R.
Modelling cell cycle synchronisation in networks of coupled radial glial cells
title Modelling cell cycle synchronisation in networks of coupled radial glial cells
title_full Modelling cell cycle synchronisation in networks of coupled radial glial cells
title_fullStr Modelling cell cycle synchronisation in networks of coupled radial glial cells
title_full_unstemmed Modelling cell cycle synchronisation in networks of coupled radial glial cells
title_short Modelling cell cycle synchronisation in networks of coupled radial glial cells
title_sort modelling cell cycle synchronisation in networks of coupled radial glial cells
topic Cell Cycle
Calcium Dynamics
Radial Glial Cells
Cell Cycle Synchronisation
Bifurcation Analysis
url https://eprints.nottingham.ac.uk/33482/
https://eprints.nottingham.ac.uk/33482/
https://eprints.nottingham.ac.uk/33482/