ZFIN ID: ZDB-PUB-140410-4
Sequential and opposing activities of Wnt and BMP coordinate zebrafish bone regeneration
Stewart, S., Gomez, A.W., Armstrong, B.E., Henner, A., and Stankunas, K.
Date: 2014
Source: Cell Reports   6(3): 482-498 (Journal)
Registered Authors: Stankunas, Kryn, Stewart, Scott
Keywords: none
MeSH Terms:
  • Animal Fins/cytology
  • Animal Fins/physiology
  • Animals
  • Bone Morphogenetic Proteins/metabolism*
  • Bone Regeneration/genetics
  • Bone Regeneration/physiology*
  • Cell Dedifferentiation/genetics
  • Cell Lineage
  • Epithelial-Mesenchymal Transition/genetics
  • Gene Expression Regulation
  • Osteoblasts/cytology
  • Osteoblasts/metabolism
  • Signal Transduction/genetics
  • Smad Proteins/metabolism
  • Wnt Proteins/metabolism*
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • beta Catenin/metabolism
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.