Fig. 1.

Neocortical development proceeds in a series of stages. During Stage 1, the neural precursor cell population expands exponentially via symmetrical cell divisions. Each mitosis generates two daughter cells that remain in the cell cycle and continue to divide. Stage 2 begins as neurons are generated from the ventricular zone (VZ). The birthday of each neuron specifies its position within the expanding cortical plate (CP). Early born neurons take up deep CP positions and are passed by later generated neurons that migrate to the superficial CP. During Stage 3, excitatory neurons generated from the dorsal VZ (cells with black nuclei) migrate radially across the intermediate zone (IZ) and into the CP along radial glial cells, whose fibers span the width of the neocortical wall from the ventricular (V) to the pial (P) surfaces. Simultaneously, inhibitory interneurons (cells with grey nuclei) generated in the ventral telencephalon migrate tangentially to integrate into the dorsal CP plate. After settling into the appropriate area and layer, neurons begin to differentiate in preparation to send and receive connections during Stage 4. Once synapse formation has begun, connections are either strengthened and refined or eliminated. During Stage 5, supernumerary cells and those not receiving the proper number and variety of synapses are removed by programmed cell death.