The G1 restriction point as critical regulator of neocortical neuronogenesis

Neuronogenesis in the pseudostratified ventricular epithelium is the initia l process in a succession of histogenetic events which give rise to the lam inate neocortex. Here we review experimental findings in mouse which suppor t the thesis that the restriction point of the G1 phase of the cell cycle i s the critical point of regulation of the overall neuronogenetic process. T he neuronogenetic interval in mouse spans 6 days. In the course of these 6 days the founder population and its progeny execute 11 cell cycles. With ea ch successive cycle there is an increase in the fraction of postmitotic cel ls which leaves the cycle (the Q fraction) and also an increase in the leng th of the cell cycle due to an increase in the length of the G1 phase of th e cycle. Q corresponds to the probability that postmitotic cells will exit the cycle at the restriction point of the G1 phase of the cell cycle. Q inc reases non-linearly, but the rate of change of Q with cycle (i.e., the firs t derivative) over the course of the neuronogenetic interval is a constant, k, which appears to be set principally by cell internal mechanisms which a re species specific. Q also seems to be modulated, but at low amplitude, by a balance of mitogenic and antimitogenic influences acting from without th e cell. We suggest that intracellular signal transduction systems control a general advance of Q during development and thereby determine the general developmental plan (i.e., cell number and laminar composition) of the neoco rtex and that external mitogens and anti-mitogens modulate this advance reg ionally and temporally and thereby produce regional modifications of the ge neral plan.