Multipotent retinal progenitor cells (RPCs) give rise to the various cell types of the vertebrate retina, from photoreceptors to glial cells. This neuronal diversity is temporally patterned: RPC competence changes over developmental time, so that cell types arise in a particular order. Cell-intrinsic temporal identity factors have been identified in the Drosophila neuroblast lineage, and some of these factors are conserved in mice to control timely production of specific retinal cell types, but the control of other cell types is poorly understood, as is the more general question of how time-restricted cell type production is achieved. Now, Michel Cayouette and colleagues reveal a critical role for the POU-homeodomain factors Pou2f1/Pou2f2 (which are homologs of Drosophila nub/pdm2) in the production of mouse cone photoreceptors. Pou2f1/2 are expressed in RPCs in early developmental stages, when cones are being produced, and artificially extending their expression to later stages leads to ectopic cone production at the expense of late-born cell types. Pou2f1 induces Pou2f2 expression, which it requires to promote cone fate, and conditional knockout of Pou2f2 in RPCs reduces cone cell number. Finally, Pou2f2 suppresses expression of the rod-inducing factor Nrl via a POU-binding motif in its promotor region. Thus, a pathway leading from Pou2f1 to Pou2f2 to Nrl ensures timely cone production.
