Zebrafish fin regeneration involves generic and regeneration-specific osteoblast injury responses

Abstract

Successful regeneration requires the coordinated execution of multiple cellular responses to injury. In amputated zebrafish fins, mature osteoblasts dedifferentiate, migrate towards the injury and form proliferative osteogenic blastema cells. We show that osteoblast migration is preceded by cell elongation and alignment along the proximodistal axis, which require actomyosin, but not microtubule turnover. Surprisingly, osteoblast dedifferentiation and migration can be uncoupled. Using pharmacological and genetic interventions, we found that NF-ĸB and retinoic acid signalling regulate dedifferentiation without affecting migration, while the complement system and actomyosin dynamics affect migration but not dedifferentiation. Furthermore, by removing bone at two locations within a fin ray, we established an injury model containing two injury sites. We found that osteoblasts dedifferentiate at and migrate towards both sites, while accumulation of osteogenic progenitor cells and regenerative bone formation only occur at the distal-facing injury. Together, these data indicate that osteoblast dedifferentiation and migration represent generic injury responses that are differentially regulated and can occur independently of each other and of regenerative growth. We conclude that successful fin bone regeneration appears to involve the coordinated execution of generic and regeneration-specific responses of osteoblasts to injury.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file.

Article and author information

Author details

  1. Ivonne Margarete Sehring

    Institute of Biochemistry and Molecular Biology, University of Ulm, Ulm, Germany
    For correspondence
    Ivonne.sehring@uni-ulm.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7812-0278
  2. Hossein Falah Mohammadi

    Institute of Biochemistry and Molecular Biology, University of Ulm, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Melanie Haffner-Luntzer

    Institute of Orthopaedic Research and Biomechanics, University Hospital Ulm, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Anita Ignatius

    Institute of Orthopaedic Research and Biomechanics, University Hospital Ulm, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4782-1979
  5. Markus Huber-Lang

    Institute of Clinical and Experimental Trauma-Immunology (ITI), University Hospital Ulm, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Gilbert Weidinger

    Institute of Biochemistry and Molecular Biology, University of Ulm, Ulm, Germany
    For correspondence
    gilbert.weidinger@uni-ulm.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3599-6760

Funding

Deutsche Forschungsgemeinschaft (Project-ID 251293561 - SFB 1149)

  • Gilbert Weidinger

Deutsche Forschungsgemeinschaft (project ID 316249678 - SFB 1279)

  • Gilbert Weidinger

Deutsche Forschungsgemeinschaft (project ID 450627322 - SFB 1506)

  • Gilbert Weidinger

Medical Faculty,Ulm University (Hertha-Nathorff-Program)

  • Ivonne Margarete Sehring

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

Reviewing Editor

  1. Céline Colnot, INSERM U955, UNIV PARIS EST CRETEIL, France

Ethics

Animal experimentation: All procedures involving animals adhered to EU directive 2010/63/EU on the protection of animals used for scientific purposes, and were approved by the state of Baden-Württemberg (Project numbers 1193 and 1494) and by local animal experiment committees. Fish of both sexes were used. Housing and husbandry followed the recommendations of the Federation of European Laboratory Animal Science Associations (FELASA) and the European Society for Fish Models in Biology and Medicine (EUFishBioMed) (Aleström et al., 2020).

Version history

  1. Received: February 4, 2022
  2. Preprint posted: February 22, 2022 (view preprint)
  3. Accepted: June 23, 2022
  4. Accepted Manuscript published: June 24, 2022 (version 1)
  5. Version of Record published: July 6, 2022 (version 2)

Copyright

© 2022, Sehring 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. Ivonne Margarete Sehring
  2. Hossein Falah Mohammadi
  3. Melanie Haffner-Luntzer
  4. Anita Ignatius
  5. Markus Huber-Lang
  6. Gilbert Weidinger
(2022)
Zebrafish fin regeneration involves generic and regeneration-specific osteoblast injury responses
eLife 11:e77614.
https://doi.org/10.7554/eLife.77614

Share this article

https://doi.org/10.7554/eLife.77614

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