PUBLICATION

Shh promotes direct interactions between epidermal cells and osteoblast progenitors to shape regenerated zebrafish bone

Authors
Armstrong, B.E., Henner, A., Stewart, S., Stankunas, K.
ID
ZDB-PUB-170330-5
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
  • Stem Cells/cytology*
  • Stem Cells/drug effects
  • Stem Cells/metabolism
  • Benzamides/pharmacology
  • Quinazolines/pharmacology
  • Basement Membrane/drug effects
  • Basement Membrane/metabolism
  • Time Factors
  • Signal Transduction/drug effects
  • Regeneration*/drug effects
  • Osteoblasts/cytology*
  • Osteoblasts/drug effects
  • Osteoblasts/metabolism
  • Transcription, Genetic/drug effects
  • Veratrum Alkaloids/pharmacology
  • Cell Communication*/drug effects
  • Calcification, Physiologic/drug effects
  • Bone Regeneration*/drug effects
  • Epidermis/cytology*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/metabolism*
  • Animal Fins/drug effects
  • Animal Fins/physiology
  • Smoothened Receptor/antagonists & inhibitors
  • Smoothened Receptor/metabolism
  • Cell Proliferation/drug effects
  • Hedgehog Proteins/metabolism*
  • Green Fluorescent Proteins/metabolism
  • Animals
  • Cell Movement/drug effects
  • Zebrafish/physiology*
(all 31)
PubMed
28351866 Full text @ Development
Abstract
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.
Genes / Markers
Figures
Figure Gallery (21 images) / 3
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
a4596TgTransgenic Insertion
    b1212TgTransgenic Insertion
      b1234TgTransgenic Insertion
        hu2131
          		Point Mutation
          sb15TgTransgenic Insertion
            vu295aTgTransgenic Insertion
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              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              No data available
              Fish
              No data available
              Antibodies
              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              ECFPEFGECFP
              EGFPEFGEGFP
              GAL4EFGGAL4
              GFPEFGGFP
              KaedeEFGKaede
              mCherryEFGmCherry
              1 - 6 of 6
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              Mapping
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              Citation
              Armstrong, B.E., Henner, A., Stewart, S., Stankunas, K. (2017) Shh promotes direct interactions between epidermal cells and osteoblast progenitors to shape regenerated zebrafish bone. Development (Cambridge, England). 144:1165-1176.