PUBLICATION

Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic expression of sonic hedgehog and bmp2b or exposure to cyclopamine

Authors
Quint, E., Smith, A., Avaron, F., Laforest, L., Miles, J., Gaffield, W., and Akimenko, M.-A.
ID
ZDB-PUB-020708-1
Date
2002
Source
Proceedings of the National Academy of Sciences of the United States of America   99(13): 8713-8718 (Journal)
Registered Authors
Akimenko, Marie-Andree, Avaron, Fabien, Laforest, Lynda, Miles, Jennifer, Quint, Elizabeth
Keywords
shh; bmp; chordin; fin regeneration; in vivo transfection
MeSH Terms
  • Animals
  • Base Sequence
  • Body Patterning*
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins/genetics*
  • Bone and Bones/embryology*
  • Cell Division/drug effects
  • DNA Primers
  • Gene Expression Regulation, Developmental*
  • Hedgehog Proteins
  • Regeneration*/drug effects
  • Signal Transduction/drug effects
  • Trans-Activators/genetics*
  • Transforming Growth Factor beta*
  • Veratrum Alkaloids/pharmacology*
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/physiology
PubMed
12060710 Full text @ Proc. Natl. Acad. Sci. USA
Abstract
Amputation of the zebrafish caudal fin stimulates regeneration of the dermal skeleton and reexpression of sonic hedgehog (shh)-signaling pathway genes. Expression patterns suggest a role for shh signaling in the secretion and patterning of the regenerating dermal bone, but a direct role has not been demonstrated. We established an in vivo method of gene transfection to express ectopically genes in the blastema of regenerating fins. Ectopic expression of shh or bmp2 in the blastema-induced excess bone deposition and altered patterning of the regenerate. The effects of shh ectopic expression could be antagonized by ectopic expression of chordin, an inhibitor of bone morphogenetic protein (bmp) signaling. We disrupted shh signaling in the regenerating fin by exposure to cyclopamine and found a dose-dependent inhibition of fin outgrowth, accumulation of melanocytes in the distal region of each fin ray, loss of actinotrichia, and reduction in cell proliferation in the mesenchyme. Morphological changes were accompanied by an expansion, followed by a reduction, in domains of shh expression and a rapid abolition of ptc1 expression. These results implicate shh and bmp2b signaling in the proliferation and/or differentiation of specialized bone-secreting cells in the blastema and suggest shh expression may be controlled by regulatory feedback mechanisms that define the region of bone secretion in the outgrowing fin.
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