Zebrafish fin regeneration involves generic and regeneration-specific osteoblast injury responses
- University of Ulm, Germany
- University Hospital Ulm, Germany
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
Ivonne Margarete Sehring
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.
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).
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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Zebrafish fin regeneration involves generic and regeneration-specific osteoblast injury responses
eLife 11:e77614.
https://doi.org/10.7554/eLife.77614
