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

Area of Science:

• Neuroscience
• Developmental Biology
• Computational Biology

Background:

• Radial glial cells are key progenitors of neocortical neurons during embryonic development.
• Intercellular communication via ATP-mediated calcium signals influences radial glial cell behavior.
• Recent findings show ATP-dependent calcium release significantly increases radial glial proliferation.

Purpose of the Study:

• To investigate the mechanisms by which ATP-mediated calcium signals regulate radial glial cell proliferation.
• To model the coupling between calcium signaling and the cell cycle in radial glial cells.
• To determine whether calcium accelerates cell cycle entry or recruits quiescent cells.

Main Methods:

• Development of a differential equation model for ATP-mediated calcium-cell cycle coupling via Cyclin D.
• Bifurcation analysis to study the model's dynamics.
• Numerical simulations of single and coupled radial glial cells.

Main Results:

• Cell cycle period shows weak dependence on cytoplasmic calcium levels.
• Calcium's direct accelerative impact on the cell cycle explains only a small portion of the observed proliferation increase.
• Bifurcation analysis indicates coexistence of stable states and an extended oscillatory region due to calcium-dependent Cyclin D dynamics.

Conclusions:

• Calcium signaling primarily recruits quiescent (G0 phase) radial glial cells onto the cell cycle.
• This recruitment mechanism is likely the main driver of calcium-induced proliferation increases at the population level.
• Coupled cell simulations support the feasibility of calcium-mediated recruitment of quiescent cells.