@article{7c2685b4924a48babe703476b1f16c24,
title = "Pou2f1 and Pou2f2 cooperate to control the timing of cone photoreceptor production in the developing mouse retina",
abstract = "Multipotent retinal progenitor cells (RPCs) generate various cell types in a precise chronological order, but how exactly cone photoreceptor production is restricted to early stages remains unclear. Here, we show that the POU-homeodomain factors Pou2f1/Pou2f2, the homologs of Drosophila temporal identity factors nub/pdm2, regulate the timely production of cones in mice. Forcing sustained expression of Pou2f1 or Pou2f2 in RPCs expands the period of cone production, whereas misexpression in late-stage RPCs triggers ectopic cone production at the expense of late-born fates. Mechanistically, we report that Pou2f1 induces Pou2f2 expression, 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 provide evidence that Pou2f1 is part of a cross-regulatory cascade with the other temporal identity factors Ikzf1 and Casz1. These results uncover Pou2f1/2 as regulators of the temporal window for cone genesis and, given their widespread expression in the nervous system, raise the possibility of a general role in temporal patterning. This article has an associated 'The people behind the papers' interview.",
keywords = "Cell fate, Mouse, Photoreceptors, Retina, Temporal patterning, Transcription",
author = "Awais Javed and Pierre Mattar and Suying Lu and Kamil Kruczek and Magdalena Kloc and Anai Gonzalez-Cordero and Rod Bremner and Ali, {Robin R.} and Michel Cayouette",
note = "Funding Information: This work was funded by grants from the Canadian Institutes of Health Research (FDN-159936) and Fighting Blindness Canada (to M.C.), the Fondation Brain Canada/Krembril Foundation (to M.C. and R.B.), as well as the UK Medical Research Council, the European Research Council and RP Fighting Blindness (to R.A.). A.J. holds a PhD scholarship from Fonds de Recherche du Qu{\'e}bec – Sant{\'e}. M.C. is an Emeritus Scholar from the Fonds de Recherche du Qu{\'e}bec – Sant{\'e} and holds the Ga{\"e}tane and Roland Pilleni{\`e} e Chair in Retina Biology from the Institut de recherches cliniques de Montr{\'e}al Foundation. Funding Information: C57BL/6J background (Mus musculus) were sacrificed at E13.5 and retinas from embryos were extracted for pCAG:Cre electroporation and ex vivo retinal explant culture. αPax6-Cre+ Pou2f2fl/fl mice were at P14 at the time of cell count analysis. The Chx10-CreERT2 mouse line was generated in Dr Takahisa Furukawa{\textquoteright}s lab (Osaka University) and provided by the RIKEN BRC through the National Bio-Resource Project of the MEXT/ AMED, Japan (RIKEN Bioresource RRID: IMSR_RBRC06574). Chx10-CreERT2+ Pou2f2fl/fl pregnant females were injected with tamoxifen at E11.5 and sacrificed at E17.5 for cell count analysis. Chx10-CreERT2+ RosatdTomato were injected with tamoxifen at E11.5 and sacrificed at E13.5. All other mouse experiments in this study were carried out on wild-type CD1 mice (Mus musculus, Charles Rivers). Publisher Copyright: {\textcopyright} 2020. Published by The Company of Biologists Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2020",
month = sep,
doi = "10.1242/dev.188730",
language = "English",
volume = "147",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "18",
}