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RESEARCH ARTICLE
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
Development 2020 147: dev188730 doi: 10.1242/dev.188730 Published 28 September 2020
Awais Javed
1Cellular Neurobiology Research Unit, Institut de recherches cliniques de Montreal (IRCM), Montreal H2W 1R7, Canada
2Molecular Biology Program, Université de Montréal, Montreal H3T 1J4, Canada
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Pierre Mattar
1Cellular Neurobiology Research Unit, Institut de recherches cliniques de Montreal (IRCM), Montreal H2W 1R7, Canada
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  • ORCID record for Pierre Mattar
Suying Lu
3Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto M5G 1X5, Canada. Department of Ophthalmology and Vision Science, Department of Lab Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada
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Kamil Kruczek
4UCL Institute of Ophthalmology, London EC1V 9EL, UK
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Magdalena Kloc
4UCL Institute of Ophthalmology, London EC1V 9EL, UK
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Anai Gonzalez-Cordero
4UCL Institute of Ophthalmology, London EC1V 9EL, UK
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Rod Bremner
3Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto M5G 1X5, Canada. Department of Ophthalmology and Vision Science, Department of Lab Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada
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Robin R. Ali
4UCL Institute of Ophthalmology, London EC1V 9EL, UK
5NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 2PD, UK
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Michel Cayouette
1Cellular Neurobiology Research Unit, Institut de recherches cliniques de Montreal (IRCM), Montreal H2W 1R7, Canada
2Molecular Biology Program, Université de Montréal, Montreal H3T 1J4, Canada
6Department of Medicine, Université de Montréal, Montreal H3T 1J4, Canada
7Department of Anatomy and Cell Biology, Division of Experimental Medicine, McGill University, Montreal H4A 3J1, Canada
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  • For correspondence: michel.cayouette@ircm.qc.ca

Handling Editor: Steve Wilson

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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.

Footnotes

  • Competing interests

    The authors declare no competing or financial interests.

  • Author contributions

    Conceptualization: A.J., P.M., M.C.; Methodology: A.J., P.M., M.C.; Formal analysis: A.J., P.M.; Investigation: A.J., P.M., S.L., K.K., M.K., A.G.-C.; Resources: R.B., R.R.A., M.C.; Writing - original draft: A.J.; Writing - review & editing: P.M., R.B., R.R.A., M.C.; Supervision: R.B., R.R.A., M.C.; Project administration: R.B., R.R.A., M.C.; Funding acquisition: R.B., R.R.A., M.C.

  • Funding

    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 Québec – Santé. M.C. is an Emeritus Scholar from the Fonds de Recherche du Québec – Santé and holds the Gaëtane and Roland Pillenière Chair in Retina Biology from the Institut de recherches cliniques de Montréal Foundation.

  • Supplementary information

    Supplementary information available online at https://dev.biologists.org/lookup/doi/10.1242/dev.188730.supplemental

  • Received January 23, 2020.
  • Accepted August 19, 2020.
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Keywords

  • Cell fate
  • Mouse
  • Photoreceptors
  • Retina
  • Temporal patterning
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RESEARCH ARTICLE
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
Development 2020 147: dev188730 doi: 10.1242/dev.188730 Published 28 September 2020
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RESEARCH ARTICLE
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
Development 2020 147: dev188730 doi: 10.1242/dev.188730 Published 28 September 2020

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