Regeneration of Amputated Zebrafish Fin Rays from De Novo Osteoblasts

• Published in: Developmental cell Vol. 22; no. 4; pp. 879 - 886
• Main Authors: Singh, Sumeet Pal, Holdway, Jennifer E., Poss, Kenneth D.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 17.04.2012; Cell Press
• Subjects: Amputation, Surgical; Animal Fins - cytology; Animal Fins - metabolism; Animals; Animals, Genetically Modified; Biological and medical sciences; Bone and Bones - cytology; Bone and Bones - metabolism; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell Lineage; Cell physiology; Danio rerio; Extremities - growth & development; Flow Cytometry; Freshwater; Fundamental and applied biological sciences. Psychology; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Molecular and cellular biology; Osteoblasts - cytology; Osteoblasts - metabolism; Regeneration - physiology; Zebrafish; Osteoarticular system; Regeneration; Vertebrata; Brachydanio rerio; Pisces; Development; Osteoblast; Bone; De novo
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2012.03.006

Determining the cellular source of new skeletal elements is critical for understanding appendage regeneration in amphibians and fish. Recent lineage-tracing studies indicated that zebrafish fin ray bone regenerates through the dedifferentiation and proliferation of spared osteoblasts, with limited if any contribution from other cell types. Here, we examined the requirement for this mechanism by using genetic ablation techniques to destroy virtually all skeletal osteoblasts in adult zebrafish fins. Animals survived this injury and restored the osteoblast population within 2 weeks. Moreover, amputated fins depleted of osteoblasts regenerated new fin ray structures at rates indistinguishable from fins possessing a resident osteoblast population. Inducible genetic fate mapping confirmed that new bone cells do not arise from dedifferentiated osteoblasts under these conditions. Our findings demonstrate diversity in the cellular origins of appendage bone and reveal that de novo osteoblasts can fully support the regeneration of amputated zebrafish fins. [Display omitted] ► Resident osteoblasts provide new bone cells to regenerating fins after amputation ► A new transgenic model for inducible osteoblast ablation and recovery in zebrafish ► Amputated fins regenerate normally after genetic depletion of osteoblasts ► De novo osteoblasts can fully support regeneration of patterned skeletal bone Following conventional amputation, zebrafish fins regenerate osteoblasts via dedifferentiation and proliferation of existing osteoblasts. Singh et al. find that transgenic ablation of osteoblasts unexpectedly allows normal regeneration via new osteoblasts emerging from nonosteoblasts. This regenerative plasticity of cell origin suggests that osteoblasts prevent other cells from becoming osteoblasts during regeneration.