Bone Regenerates via Dedifferentiation of Osteoblasts in the Zebrafish Fin

• Published in: Developmental cell Vol. 20; no. 5; pp. 713 - 724
• Main Authors: Knopf, Franziska, Hammond, Christina, Chekuru, Avinash, Kurth, Thomas, Hans, Stefan, Weber, Christopher W., Mahatma, Gina, Fisher, Shannon, Brand, Michael, Schulte-Merker, Stefan, Weidinger, Gilbert
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 17.05.2011; Cell Press
• Subjects: Animal Fins - cytology; Animal Fins - metabolism; Animals; Biological and medical sciences; Bone and Bones - cytology; Bone and Bones - metabolism; Cell Dedifferentiation; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Danio rerio; Down-Regulation; Freshwater; Fundamental and applied biological sciences. Psychology; Molecular and cellular biology; Osteoblasts - cytology; Osteoblasts - metabolism; Zebrafish; Osteoarticular system; Vertebrata; Brachydanio rerio; Pisces; Development; Osteoblast; Bone
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2011.04.014

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. ► Mature osteoblasts dedifferentiate in response to fin amputation ► Dedifferentiated osteoblasts proliferate and migrate to form part of the blastema ► Osteoblasts remain lineage restricted throughout regeneration