ZFIN ID: ZDB-PUB-150809-8
Retinoic acid signaling spatially restricts osteoblasts and controls ray-interray organization during zebrafish fin regeneration
Blum, N., Begemann, G.
Date: 2015
Source: Development (Cambridge, England)   142(17): 2888-93 (Journal)
Registered Authors: Begemann, Gerrit, Blum, Nicola
Keywords: Cyp26a1, Caudal fin, Zebrafish, Regeneration, Osteoblast, Interray
MeSH Terms:
  • Animal Fins/cytology*
  • Animal Fins/drug effects
  • Animal Fins/physiology*
  • Animals
  • Cell Proliferation/drug effects
  • Cytochrome P-450 Enzyme System/metabolism
  • Epidermis/drug effects
  • Epidermis/metabolism
  • Fibroblast Growth Factors/pharmacology
  • Hedgehog Proteins/metabolism
  • Models, Biological
  • Osteoblasts/cytology
  • Osteoblasts/drug effects
  • Osteoblasts/metabolism*
  • Regeneration*/drug effects
  • Signal Transduction*/drug effects
  • Tretinoin/metabolism*
  • Zebrafish/physiology*
  • Zebrafish Proteins/metabolism
PubMed: 26253402 Full text @ Development
The zebrafish caudal fin consists of repeated units of bony rays separated by soft interray tissue, an organization that must be faithfully reestablished during fin regeneration. How and why regenerating rays respect ray-interray boundaries, thus extending only the existing bone, has remained unresolved. Here, we demonstrate that a retinoic acid (RA)-degrading niche is established by Cyp26a1 in the proximal basal epidermal layer that orchestrates ray-interray organization by spatially restricting osteoblasts. Disruption of this niche causes preosteoblasts to ignore ray-interray boundaries and to invade neighboring interrays where they form ectopic bone. Concomitantly, non-osteoblastic blastema cells and regenerating blood vessels spread into the interrays, resulting in overall disruption of ray-interray organization and irreversible inhibition of fin regeneration. The cyp26a1-expressing niche plays another important role during subsequent regenerative outgrowth, where it facilitates the Shha-promoted proliferation of osteoblasts. Finally, we show that the previously observed distal shift of ray bifurcations in regenerating fins upon RA treatment, or amputation close to the bifurcation, can be explained by inappropriate preosteoblast alignment and does not necessarily require putative changes in proximodistal information. Our findings uncover a mechanism regulating preosteoblast alignment and maintenance of ray-interray boundaries during fin regeneration.