Fig. 5. Cell cycle length, asymmetric cell division and cell fate determination – a model. In our model, a molecule capable of inducing a cell fate change (cell fate determinant) is assumed to be distributed unequally upon mitosis, e.g. with daughter cell A receiving 60% and daughter cell B 40% of this determinant (arrows). For a cell fate change to occur, the effect of the cell fate determinant has to reach a threshold (dashed line), i.e. the cell fate determinant needs to act for a certain length of time (for example, a transcription factor activating transcription until a certain amount of gene product has been produced). Given the unequal amounts of cell fate determinant in cells A and B, this threshold will be reached by neither cell A nor cell B after one unit of time, by cell A but not cell B after two units of time, and by both cell A and cell B after three units of time. If the cell fate determinant would, for example, be able to induce the switch of NE cells from a proliferative to a neuron-generating division, neither NE cell would switch to neurogenesis if the length of the critical phase of the cell cycle corresponded to one time unit, NE cell A but not NE cell B would switch upon doubling this phase, and both NE cells would switch upon tripling it. Hence, an unequal distribution of a cell fate determinant upon mitosis will only lead to an asymmetric daughter cell fate if the length of the cell cycle is appropriate. Moreover, if early in G1, the cell fate determinant were to drive the production of a molecule that causes cell cycle arrest upon reaching the threshold, depending on the length of G1 either none, one or both of the daughter cells would acquire a post-mitotic state (i.e. turning G1 into G0), as is characteristic of neurons. Note that the basic principle of the model, i.e. the dependence of cell fate on time, holds true for any cell, irrespective of asymmetric division. Moreover, the model can be adopted to two cells being exposed to different concentrations of an extracellular factor affecting cell fate, or to two cells being exposed to the same concentration of such a factor for different times.