Fig. 6. A model for V_mem regulation of apoptosis-proliferation balance towards shaping brain morphology.

Model for V_mem regulation of brain tissue sculpting. Both dorsal and ventral V_mem signals are involved in brain tissue sculpting by their effects on the balance of apoptosis and proliferation within the tissue. Under normal conditions (i) the dorsal V_mem strongly inhibits apoptosis and mildly stimulates proliferation locally within the developing brain. The ventral V_mem strongly inhibits proliferation and mildly stimulates apoptosis at a distance in the developing brain tissue. Coordination of these two V_mem signals results in proper balance of proliferation-apoptosis and ultimately sculpting of the brain tissue during development. Blocking of dorsal V_mem signal (ii) releases the strong inhibition on apoptosis and further facilitates strong inhibition of proliferation by the ventral V_mem signals. This results in a shift in balance towards apoptosis resulting in malformed brain tissue. Blocking of ventral V_mem signal (iii) releases the strong inhibition on proliferation and increases the inhibition of apoptosis by the dorsal V_mem signal. This results in significant increase in proliferating cells but otherwise largely normal brain structure development. Blocking of both dorsal and ventral V_mem signal (iv) cancel each other’s effect on proliferation and apoptosis leaving the sculpting of brain to other regulators of brain structure development resulting in largely normal brain structure.