Cyclin E-p27 opposition and regulation of the G1 phase of the cell cycle in the murine neocortical PVE: A quantitative analysis of mRNA in situ hybridization

We have analyzed the expression patterns of mRNAs of five cell cycle relate d proteins in the ventricular zone of the neocortical cerebral wall over th e course of the neuronogenetic interval in the mouse. One set of mRNAs (cyc lin E and p21) are initially expressed at high levels but expression then f alls to a low asymptote. A second set (p27, cyclin B and cdk2) are initiall y expressed at low levels but ascend to peak levels only to decline again. These patterns divide the overall neuronogenetic interval into three phases . In phase 1 cyclin E and p21 levels of mRNA expression are high, while tho se of mRNAs of p27, cdk2 and cyclin B are low. In this phase the fraction o f cells leaving the cycle after each mitosis, Q, is low and the duration of the G1 phase, T-G1, is short. In phase 2 levels of expression of cyclin E and p21 fall to asymptote while levels of expression of mRNA of the other t hree proteins reach their peaks. Q increases to approach 0.5 and T-G1 incre ases even more rapidly to approach its maximum length. In phase 3 levels of expression of cyclin E and p21 mRNAs remain low and those of the mRNAs of the other three proteins fall. T-G1 becomes maximum and a rapidly increases to 1.0. The character of these phases can be understood in part as consequ ences of the reciprocal regulatory influence of p27 and cyclin E and of the rate limiting functions of p27 at the restriction point and of cyclin E at the G1 to S transition.