ZFIN ID: ZDB-PUB-170330-5
Shh promotes direct interactions between epidermal cells and osteoblast progenitors to shape regenerated zebrafish bone
Armstrong, B.E., Henner, A., Stewart, S., Stankunas, K.
Date: 2017
Source: Development (Cambridge, England)   144: 1165-1176 (Journal)
Registered Authors: Stankunas, Kryn, Stewart, Scott
Keywords: BMS-833923, Basal epidermis, Basement membrane, Bone patterning, Calcification, Caudal fins, Cyclopamine, Hedgehog signaling, Indian hedgehog, Osteoblasts, Ray branching, Regeneration, Smoothened inhibitor, Sonic hedgehog, Zebrafish
MeSH Terms:
  • Animal Fins/drug effects
  • Animal Fins/physiology
  • Animals
  • Basement Membrane/drug effects
  • Basement Membrane/metabolism
  • Benzamides/pharmacology
  • Bone Regeneration*/drug effects
  • Calcification, Physiologic/drug effects
  • Cell Communication*/drug effects
  • Cell Movement/drug effects
  • Cell Proliferation/drug effects
  • Epidermis/cytology*
  • Green Fluorescent Proteins/metabolism
  • Hedgehog Proteins/metabolism*
  • Osteoblasts/cytology*
  • Osteoblasts/drug effects
  • Osteoblasts/metabolism
  • Quinazolines/pharmacology
  • Regeneration*/drug effects
  • Signal Transduction/drug effects
  • Smoothened Receptor/antagonists & inhibitors
  • Smoothened Receptor/metabolism
  • Stem Cells/cytology*
  • Stem Cells/drug effects
  • Stem Cells/metabolism
  • Time Factors
  • Transcription, Genetic/drug effects
  • Veratrum Alkaloids/pharmacology
  • Zebrafish/physiology*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/metabolism*
PubMed: 28351866 Full text @ Development
Zebrafish innately regenerate amputated fins by mechanisms that expand and precisely position injury-induced progenitor cells to re-form tissue of the original size and pattern. For example, cell signaling networks direct osteoblast progenitors (pObs) to rebuild thin cylindrical bony rays with a stereotypical branched morphology. Hedgehog/Smoothened (Hh/Smo) signaling has been variably proposed to stimulate overall fin regenerative outgrowth or promote ray branching. Using a photoconvertible patched2 reporter, we resolve active Hh/Smo output to a narrow distal regenerate zone comprising pObs and adjacent motile basal epidermal cells. This Hh/Smo activity is driven by epidermal Sonic hedgehog a (Shha) rather than Ob-derived Indian hedgehog a (Ihha), which nevertheless functions atypically to support bone maturation. Using BMS-833923, a uniquely effective Smo inhibitor, and high-resolution imaging, we show that Shha/Smo is functionally dedicated to ray branching during fin regeneration. Hh/Smo activation enables transiently divided clusters of Shha-expressing epidermis to escort pObs into similarly split groups. This co-movement likely depends on epidermal cellular protrusions that directly contact pObs only where an otherwise occluding basement membrane remains incompletely assembled. Progressively separated pObs pools then continue regenerating independently to collectively re-form a now branched skeletal structure.