Research Paper Volume 8, Issue 7 pp 1540—1570

Figure 2. Mathematical modeling of forebrain growth. (A) Hypothetical models of forebrain growth. Various possible explanations of forebrain growth in CCNA2^fl/fl, Nestin-cre brains are presented. (B) Schematic of the fates of a radial glia neural stem cell in our model. Radial glia can divide in (1) a symmetric self-renewal, (2) an asymmetric self-renewal generating a migratory neuron and a radial glia, or (3) an asymmetric, non-renewing division generating a migratory neuron and an intermediate progenitor, with the intermediate progenitor dividing into two migratory neurons. (C) Diagram of cell cycle progression corresponding to our mathematical model. Cells leave each phase of the cell cycle at different rates J(.) depending on population size and mitotic age. These parameters are described in Supplemental Table S4. Cells are also able to enter an apoptotic state from each phase. The flows between the cell cycle phases for each type of division in (A) are noted by J, J′, J′′, or J_IP. (D) Computed volumes of the VZ and combined VZ/SVZ for CCNA2^fl/fl, Nestin-cre and control simulations. The control VZ volume plateaus at approximately E15, whereas it continues to grow in the CCNA2^fl/fl, Nestin-cre until E15.5. Similar trends are seen in the combined VZ/SVZ volumes. The x-axis is the embryonic day, and the y-axis is the volume of the VZ or combined VZ/SVZ. (E) The cumulative neuronal output of the VZ/SVZ during E14.5-E17.5 of the CCNA2^fl/fl, Nestin-cre simulations trails that of the control throughout the time period. The x-axis is embryonic day, and the y-axis is total neuronal volume.