FIGURE 3.

Simplified model on the coordination of G₁ dynamics by extrinsic signals and their integration into fate decisions based on evidence from cyclin and CDK manipulation studies. (A) Fast proliferation is achieved in presence of high mitogen levels that stimulate the expression of D-cyclins, thus initiating the canonical CC cascade driving progression through G₁. If cells pass the R-point (point of no return), mitogen stimulation is no longer required for commencing cell division. D-cyclin levels stay high until mitogens are withdrawn. (B) If specification signals come on board, CKIs increase on top and restrain but don’t block the activities of D-cyclins, resulting in a lengthening of G₁. This, as proposed by the “cell cycle length theory,” provides sufficient time for specification signals to initiate the differentiation program before cells reach the R-point. (C) If mitogens decrease, D-cyclins become rapidly degraded and cells can not overcome the R-point. Adult NSCs then return into a reversible quiescent state (G₀), whereas cells that initiated their differentiation program terminally exit the cell cycle to become an immature neuron (IN).