Pou2f1 and Pou2f2 cooperate to control the timing of cone photoreceptor production in the developing mouse retina
Development. 2020 Sep 28;147(18):dev188730. doi: 10.1242/dev.188730.
Awais Javed, Pierre Mattar, Suying Lu, Kamil Kruczek, Magdalena Kloc, Anai Gonzalez-Cordero, Rod Bremner, Robin R Ali, Michel Cayouette
Multipotent retinal progenitor cells (RPCs) generate different cell types in a precise chronological order, but exactly how cone photoreceptor production is restricted to early stages remains unclear. Here, we show that the POU homeodomain factors Pou2f1/Pou2f2, homologs of the Drosophila temporal identity factors nub/pdm2, regulate timely cone production in mice. Enforcing sustained expression of Pou2f1 or Pou2f2 in RPCs prolongs the cone production period, whereas misexpression in late-stage RPCs triggers ectopic cone production at the expense of the late fate. Mechanistically, we report that Pou2f1 induces the expression of Pou2f2, which binds to a POU motif in the promoter of the rod-inducing factor Nrl to repress its expression. Conversely, conditional inactivation of Pou2f2 in RPCs increases Nrl expression and reduces cone production. Finally, we show that Pou2f1 is part of a cross-regulatory cascade with the other temporal identity factors Ikzf1 and Casz1. These results reveal that Pou2f1/2 is a regulator of the temporal window of cone genesis and, given their widespread expression in the nervous system, raise the possibility of a general role in temporal patterning.
