Cell cycle as operational unit of neocortical neuronogenesis

Neuronogenesis in the ventricular epithelium is the initial process in a succession of histogenetic events that give rise to the laminate neocortex. Herein, we review experimental findings in mouse that support the thesis that cell cycle is the operational unit of the neuronogenetic sequence. We show that the principal regulated parameters of proliferation progress uniformly as functions of cycle number and are independent of location in the proliferative epithelium. These parameters are the duration of the G₁ phase of the cell cycle and Q, the fraction of cells that leaves the cycle after mitosis. Furthermore, the specification of neuronal class and possibly also specification of a regional protomap occur coordinately with cell cycle across the expanse of the proliferative epithelium. This coordinate progression of histogenetic events with cell cycles invites the hypothesis that the mechanisms of cell cycle regulation are interdependent in proliferative cells.