Pou2f1 and Pou2f2 cooperate to control the timing of cone photoreceptor production in the developing mouse retina

Awais Javed, Pierre Mattar, Suying Lu, Kamil Kruczek, Magdalena Kloc, Anai Gonzalez-Cordero, Rod Bremner, Robin R. Ali, Michel Cayouette*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

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.

Original languageEnglish
Article numberdev188730
JournalDevelopment (Cambridge)
Volume147
Issue number18
DOIs
Publication statusPublished - Sept 2020

Keywords

  • Cell fate
  • Mouse
  • Photoreceptors
  • Retina
  • Temporal patterning
  • Transcription

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