1. Developmental Biology
  2. Stem Cells and Regenerative Medicine
Download icon

Hierarchical stem cell topography splits growth and homeostatic functions in the fish gill

  1. Julian Stolper
  2. Elizabeth Mayela Ambrosio
  3. Diana-Patricia Danciu
  4. Lorena Buono
  5. David A Elliott
  6. Kiyoshi Naruse
  7. Juan R Martínez-Morales
  8. Anna Marciniak-Czochra
  9. Lazaro Centanin  Is a corresponding author
  1. Centre for Organismal Studies, Heidelberg University, Germany
  2. Heidelberg University, Germany
  3. Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, Spain
  4. Murdoch Children's Research Institute, Royal Children's Hospital, Australia
  5. National Institute for Basic Biology, National Institutes of Natural Sciences, Japan
Research Article
  • Cited 0
  • Views 1,812
  • Annotations
Cite this article as: eLife 2019;8:e43747 doi: 10.7554/eLife.43747

Abstract

While lower vertebrates contain adult stem cells (aSCs) that maintain homeostasis and drive un-exhaustive organismal growth, mammalian aSCs display mainly the homeostatic function. Here we use lineage analysis in the fish gill to address aSCs and report separate stem cell populations for homeostasis and growth. These aSCs are fate-restricted during the entire post-embryonic life and even during re-generation paradigms. We use chimeric animals to demonstrate that p53 mediates growth coordination among fate-restricted aSCs, suggesting a hierarchical organisation among lineages in composite organs like the fish gill. Homeostatic and growth aSCs are clonal but differ in their topology; modifications in tissue architecture can convert the homeostatic zone into a growth zone, indicating a leading role for the physical niche defining stem cell output. We hypothesise that physical niches are main players to restrict aSCs to a homeostatic function in animals with fixed adult size.

Article and author information

Author details

  1. Julian Stolper

    Animal Physiology and Development, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Elizabeth Mayela Ambrosio

    Animal Physiology and Development, 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:" 0000-0001-7227-7744
  3. Diana-Patricia Danciu

    Institute of Applied Mathematics, 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:" 0000-0002-8683-3956
  4. Lorena Buono

    Gene Regulation and Morphogenesis, Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, Seville, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. David A Elliott

    Cell Biology, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1052-7407
  6. Kiyoshi Naruse

    Laboratory of Bioresources, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki, Japan
    Competing interests
    The authors declare that no competing interests exist.
  7. Juan R Martínez-Morales

    Gene Regulation and Morphogenesis, Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, Seville, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4650-4293
  8. Anna Marciniak-Czochra

    Institute of Applied Mathematics, 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:" 0000-0002-5831-6505
  9. Lazaro Centanin

    Animal Physiology and Development, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    For correspondence
    lazaro.centanin@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:" 0000-0003-3889-4524

Funding

Deutsche Forschungsgemeinschaft (SFB873/A11)

  • Lazaro Centanin

Deutsche Forschungsgemeinschaft (SFB873/B08)

  • Anna Marciniak-Czochra

University of Melbourne (Melbourne Research Fellowship / Graduate Student Fellowship)

  • Julian Stolper

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

Ethics

Animal experimentation: Experimental procedures with fish were performed in accordance with 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), and with the approval from the Institutional Animal Care and Use Committees of the National Institute for Basic Biology, Japan.

Reviewing Editor

  1. Alejandro Sánchez Alvarado, Stowers Institute for Medical Research, United States

Publication history

  1. Received: November 19, 2018
  2. Accepted: May 14, 2019
  3. Accepted Manuscript published: May 15, 2019 (version 1)
  4. Accepted Manuscript updated: May 16, 2019 (version 2)
  5. Version of Record published: May 24, 2019 (version 3)

Copyright

© 2019, Stolper 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.

Metrics

  • 1,812
    Page views
  • 147
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Developmental Biology
    2. Medicine
    Md Rakibul Hasan et al.
    Research Article Updated

    Mutations in the gene encoding Ras-associated binding protein 23 (RAB23) cause Carpenter Syndrome, which is characterized by multiple developmental abnormalities including polysyndactyly and defects in skull morphogenesis. To understand how RAB23 regulates skull development, we generated Rab23-deficient mice that survive to an age where skeletal development can be studied. Along with polysyndactyly, these mice exhibit premature fusion of multiple sutures resultant from aberrant osteoprogenitor proliferation and elevated osteogenesis in the suture. FGF10-driven FGFR1 signaling is elevated in Rab23-/-sutures with a consequent imbalance in MAPK, Hedgehog signaling and RUNX2 expression. Inhibition of elevated pERK1/2 signaling results in the normalization of osteoprogenitor proliferation with a concomitant reduction of osteogenic gene expression, and prevention of craniosynostosis. Our results suggest a novel role for RAB23 as an upstream negative regulator of both FGFR and canonical Hh-GLI1 signaling, and additionally in the non-canonical regulation of GLI1 through pERK1/2.

    1. Developmental Biology
    Noriko Ichino et al.
    Tools and Resources

    One key bottleneck in understanding the human genome is the relative under-characterization of 90% of protein coding regions. We report a collection of 1,200 transgenic zebrafish strains made with the gene-break transposon (GBT) protein trap to simultaneously report and reversibly knockdown the tagged genes. Protein trap-associated mRFP expression shows previously undocumented expression of 35% and 90% of cloned genes at 2 and 4 days post-fertilization, respectively. Further, investigated alleles regularly show 99% gene-specific mRNA knockdown. Homozygous GBT animals in ryr1b, fras1, tnnt2a, edar and hmcn1 phenocopied established mutants. 204 cloned lines trapped diverse proteins, including 64 orthologs of human disease-associated genes with 40 as potential new disease models. Severely reduced skeletal muscle Ca2+ transients in GBT ryr1b homozygous animals validated the ability to explore molecular mechanisms of genetic diseases. This GBT system facilitates novel functional genome annotation towards understanding cellular and molecular underpinnings of vertebrate biology and human disease.