Retinal stem cells modulate proliferative parameters to coordinate post-embryonic morphogenesis in the eye of fish
- Heidelberg University, Germany
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
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).
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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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
