PUBLICATION

Heat-shock protein 60 is required for blastema formation and maintenance during regeneration

Authors
Makino, S., Whitehead, G.G., Lien, C.L., Kim, S., Jhawar, P., Kono, A., Kawata, Y., and Keating, M.T.
ID
ZDB-PUB-051012-3
Date
2005
Source
Proceedings of the National Academy of Sciences of the United States of America   102(41): 14599-14604 (Journal)
Registered Authors
Keating, Mark T., Lien, Ching-Ling (Ellen), Makino, Shinji, Whitehead, Geoff
Keywords
blastema, regeneration, zebrafish, genetics, stress response
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Apoptosis/genetics
  • Blotting, Northern
  • Bromodeoxyuridine
  • Cell Proliferation*
  • Chaperonin 60/genetics*
  • Chaperonin 60/metabolism*
  • Chromosome Mapping
  • DNA Mutational Analysis
  • DNA Primers
  • Extremities/physiology*
  • Immunohistochemistry
  • In Situ Hybridization
  • Microscopy, Electron
  • Molecular Sequence Data
  • Mutation, Missense/genetics
  • Regeneration/physiology*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Zebrafish/physiology*
PubMed
16204379 Full text @ Proc. Natl. Acad. Sci. USA
Abstract
Zebrafish fin regeneration requires the formation and maintenance of blastema cells. Blastema cells are not derived from stem cells but behave as such, because they are slow-cycling and are thought to provide rapidly proliferating daughter cells that drive regenerative outgrowth. The molecular basis of blastema formation is not understood. Here, we show that heat-shock protein 60 (hsp60) is required for blastema formation and maintenance. We used a chemical mutagenesis screen to identify no blastema (nbl), a zebrafish mutant with an early fin regeneration defect. Fin regeneration failed in nbl due to defective blastema formation. nbl also failed to regenerate hearts. Positional cloning and mutational analyses revealed that nbl results from a V324E missense mutation in hsp60. This mutation reduced hsp60 function in binding and refolding denatured proteins. hsp60 expression is increased during formation of blastema cells, and dysfunction leads to mitochondrial defects and apoptosis in these cells. These data indicate that hsp60 is required for the formation and maintenance of regenerating tissue.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes