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

Shinji Makino, Geoffrey G. Whitehead, Ching Ling Lien, Soo Kim, Payal Jhawar, Akane Kono, Yasushi Kawata, Mark T. Keating

研究成果: Article査読

76 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)14599-14604
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
102
41
DOI
出版ステータスPublished - 2005 10 11
外部発表はい

ASJC Scopus subject areas

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