Retinal stem cells modulate proliferative parameters to coordinate post-embryonic morphogenesis in the eye of fish

Abstract

Combining clonal analysis with a computational agent based model, we investigate how tissue-specific stem cells for neural retina (NR) and retinal pigmented epithelium (RPE) of the teleost medaka (Oryzias latipes) coordinate their growth rates. NR cell division timing is less variable, consistent with an upstream role as growth inducer. RPE cells divide with greater variability, consistent with a downstream role responding to inductive signals. Strikingly, the arrangement of the retinal ciliary marginal zone niche results in a spatially biased random lineage loss, where stem- and progenitor cell domains emerge spontaneously. Further, our data indicate that NR cells orient division axes to regulate organ shape and retinal topology. We highlight an unappreciated mechanism for growth coordination, where one tissue integrates cues to synchronize growth of nearby tissues. This strategy may enable evolution to modulate cell proliferation parameters in one tissue to adapt whole-organ morphogenesis in a complex vertebrate organ.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 3; 4; 5; 6.Model description and list of parameters are in the appendix.EPISIM Modeller project archive and EPISIM Simulator executable as well asinstructions for use have been provided as supplementary files.The relevant parts of the source code containing the implementation of the model as described in the appendix have been provided as supplementary files.The full source code of EPISIM Simulator is available at: https://gitlab.com/EPISIM/EPISIM-Simulator

Article and author information

Author details

  1. Erika Tsingos

    Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    For correspondence
    Erika.tsingos@cos.uni-heidelberg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7267-160X
  2. Burkhard Höckendorf

    Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Thomas Sütterlin

    National Center for Tumor Diseases, Hamamatsu TIGA Center, Bioquant, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Stephan Kirchmaier

    Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Niels Grabe

    National Center for Tumor Diseases, Hamamatsu TIGA Center, Bioquant, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Lazaro Centanin

    Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3889-4524
  7. Joachim Wittbrodt

    Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    For correspondence
    jochen.wittbrodt@cos.uni-heidelberg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8550-7377

Funding

7th framework program of the European Union (ERC advanced grant GA 294354-ManISteC)

  • Joachim Wittbrodt

Research Training Group Mathematical Modelling for the Quantitative Biosciences

  • Niels Grabe

Heidelberg Biosciences International Graduate School HBIGS (MSc/PhD fellowship)

  • Erika Tsingos

Joachim Herz Stiftung (Add-On Fellowship for Interdisciplinary Science)

  • Erika Tsingos

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

Ethics

Animal experimentation: All experimental procedures were performed according to the guidelines of the German animal welfare law and approved by the local government (Tierschutzgesetz {section sign}11, Abs. 1, Nr. 1, husbandry permit number AZ 35-9185.64/BH; line generation permit number AZ 35-9185.81/G-145-15).

Reviewing Editor

  1. Raymond E Goldstein, University of Cambridge, United Kingdom

Publication history

  1. Received: October 7, 2018
  2. Accepted: March 13, 2019
  3. Accepted Manuscript published: March 26, 2019 (version 1)
  4. Version of Record published: April 26, 2019 (version 2)

Copyright

© 2019, Tsingos 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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  1. Erika Tsingos
  2. Burkhard Höckendorf
  3. Thomas Sütterlin
  4. Stephan Kirchmaier
  5. Niels Grabe
  6. Lazaro Centanin
  7. Joachim Wittbrodt
(2019)
Retinal stem cells modulate proliferative parameters to coordinate post-embryonic morphogenesis in the eye of fish
eLife 8:e42646.
https://doi.org/10.7554/eLife.42646

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