Figure 10

Models of Ccnd1 function in the retina. (A) General model of Ccnd1-dependence in retinal progenitor cells (RPCs). Most, if not all RPCs express CCND1. At least one division before cell cycle exit, RPCs become dependent on CCND1 to remain in the cell cycle (RPCs in gray box). Those that retain sufficiently high Ccnd1 levels or activity continue to divide whereas those that drop below a threshold will produce at least one post-mitotic precursor cell (P). It is not known if the other daughters of each division are Ccnd1-dependent, nor is the mode of division known for Ccnd1-dependent RPCs. It is presumed that at least some of the RPCs that persist contribute to the RPC population at later stages. (B) Model of how cell production is altered in the absence of Ccnd1 during early retinal development. In the wild-type retina, a proportion of CCND1-dependent RPCs will produce precursors that differentiate into cone, horizontal, or amacrine cells (O/P). In the Ccnd1^-/- retina, Ccnd1-dependent RPCs exit at least one division sooner, resulting in a gradual reduction in the size of the RPC population and an enhancement in the relative production of retinal ganglion cell (RGC) precursors at the expense of other precursor types. This could be due to an instructive role for Ccnd1 in cell fate specification or to a consequence of RPC competence and/or altered environment at the time of exit. The inability of RPCs to replenish the PTF1A precursor population (as it does for the OTX2 precursor population) suggests that most RPCs lose their competence to make PTF1A precursors (R*). Similar mechanisms may influence the output of other precursor populations.