1. Developmental Biology
  2. Genetics and Genomics
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OTX2 represses sister cell fate choices in the developing retina to promote photoreceptor specification

Research Article
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Cite this article as: eLife 2020;9:e54279 doi: 10.7554/eLife.54279

Abstract

During vertebrate retinal development, subsets of progenitor cells produce progeny in a non-stochastic manner, suggesting that these decisions are tightly regulated. However, the gene-regulatory network components that are functionally important in these progenitor cells are largely unknown. Here we identify a functional role for the OTX2 transcription factor in this process. CRISPR/Cas9 gene editing was used to produce somatic mutations of OTX2 in the chick retina and identified similar phenotypes to those observed in human patients. Single cell RNA sequencing was used to determine the functional consequences OTX2 gene editing on the population of cells derived from OTX2-expressing retinal progenitor cells. This confirmed that OTX2 is required for the generation of photoreceptors, but also for repression of specific retinal fates and alternative gene regulatory networks. These include specific subtypes of retinal ganglion and horizontal cells, suggesting that in this context, OTX2 functions to repress sister cell fate choices.

Data availability

Sequencing data have been deposited in GEO under accession code GSE142244

The following data sets were generated

Article and author information

Author details

  1. Miruna Georgina Ghinia Tegla

    Biology, The City College of New York, CUNY, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Diego F Buenaventura

    Biology, The City College of New York, CUNY, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Diana Y Kim

    Biology, The City College of New York, CUNY, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Cassandra Thakurdin

    Biology, The City College of New York, CUNY, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Kevin C Gonzalez

    Biology, The City College of New York, CUNY, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Mark M Emerson

    Biology, The City College of New York, CUNY, New York, United States
    For correspondence
    memerson@ccny.cuny.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1914-5782

Funding

National Eye Institute (R01EY024982)

  • Mark M Emerson

National Institute of General Medical Sciences (T34GM007639)

  • Kevin C Gonzalez

National Institute on Minority Health and Health Disparities (3G12MD007603)

  • Miruna Georgina Ghinia Tegla
  • Diego F Buenaventura
  • Diana Y Kim
  • Cassandra Thakurdin
  • Kevin C Gonzalez
  • Mark M Emerson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Claude Desplan, New York University, United States

Publication history

  1. Received: December 9, 2019
  2. Accepted: April 28, 2020
  3. Accepted Manuscript published: April 29, 2020 (version 1)
  4. Version of Record published: May 19, 2020 (version 2)

Copyright

© 2020, Ghinia Tegla et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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