Bone regenerates via dedifferentiation of osteoblasts in the zebrafish fin

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

While mammals have a limited capacity to repair bone defects, zebrafish can completely regenerate amputated bony structures of their fins. Fin regeneration is dependent on formation of a blastema, a progenitor cell pool accumulating at the amputation plane. It is unclear which cells the blastema is derived from, whether it forms by dedifferentiation of mature cells, and whether blastema cells are multipotent. We show that mature osteoblasts dedifferentiate and form part of the blastema. Osteoblasts downregulate expression of intermediate and late bone differentiation markers and induce genes expressed by bone progenitors. Dedifferentiated osteoblasts proliferate in a FGF-dependent manner and migrate to form part of the blastema. Genetic fate mapping shows that osteoblasts only give rise to osteoblasts in the regenerate, indicating that dedifferentiation is not associated with the attainment of multipotency. Thus, bone can regenerate from mature osteoblasts via dedifferentiation, a finding with potential implications for human bone repair.

Details

Original languageEnglish
Pages (from-to)713-724
Number of pages12
JournalDevelopmental Cell
Volume20
Issue number5
Publication statusPublished - 17 May 2011
Peer-reviewedYes

External IDs

Scopus 79955926225
PubMed 21571227
ORCID /0000-0001-5624-1717/work/142238990
ORCID /0000-0002-0420-7477/work/142250377
ORCID /0000-0003-0283-0211/work/142257318

Keywords

Keywords

  • Animal Fins/cytology, Animals, Bone and Bones/cytology, Cell Dedifferentiation, Down-Regulation, Osteoblasts/cytology, Zebrafish