Sequential and opposing activities of Wnt and BMP coordinate zebrafish bone regeneration
- Authors
- Stewart, S., Gomez, A.W., Armstrong, B.E., Henner, A., and Stankunas, K.
- ID
- ZDB-PUB-140410-4
- Date
- 2014
- Source
- Cell Reports 6(3): 482-498 (Journal)
- Registered Authors
- Stankunas, Kryn, Stewart, Scott
- Keywords
- none
- MeSH Terms
-
- Cell Lineage
- Epithelial-Mesenchymal Transition/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Cell Dedifferentiation/genetics
- PubMed
- 24485659 Full text @ Cell Rep.
Zebrafish fully regenerate lost bone, including after fin amputation, through a process mediated by dedifferentiated, lineage-restricted osteoblasts. Mechanisms controlling the osteoblast regenerative program from its initiation through reossification are poorly understood. We show that fin amputation induces a Wnt/β-catenin-dependent epithelial to mesenchymal transformation (EMT) of osteoblasts in order to generate proliferative Runx2+ preosteoblasts. Localized Wnt/β-catenin signaling maintains this progenitor population toward the distal tip of the regenerative blastema. As they become proximally displaced, preosteoblasts upregulate sp7 and subsequently mature into re-epithelialized Runx2/sp7+ osteoblasts that extend preexisting bone. Autocrine bone morphogenetic protein (BMP) signaling promotes osteoblast differentiation by activating sp7 expression and counters Wnt by inducing Dickkopf-related Wnt antagonists. As such, opposing activities of Wnt and BMP coordinate the simultaneous demand for growth and differentiation during bone regeneration. This hierarchical signaling network model provides a conceptual framework for understanding innate bone repair and regeneration mechanisms and rationally designing regenerative therapeutics.
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