hdac activity is required during xenopus tail regeneration在非洲爪蟾蜍尾再生hdac活性是必需的.pdfVIP

HDAC Activity Is Required during Xenopus Tail Regeneration 1. ´ 2. 1 1 Ai-Sun Tseng , Katia Carneiro , Joan M. Lemire , Michael Levin * 1 Department of Developmental Biology, Center for Regenerative and Developmental Biology, Tufts University, Medford, Massachusetts, United States of America, 2 Department of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Abstract The ability to fully restore damaged or lost organs is present in only a subset of animals. The Xenopus tadpole tail is a complex appendage, containing epidermis, muscle, nerves, spinal cord, and vasculature, which regenerates after amputation. Understanding the mechanisms of tail regeneration may lead to new insights to promote biomedical regeneration in non-regenerative tissues. Although chromatin remodeling is known to be critical for stem cell pluripotency, its role in complex organ regeneration in vivo remains largely uncharacterized. Here we show that histone deacetylase (HDAC) activity is required for the early stages of tail regeneration. HDAC1 is expressed during the 1st two days of regeneration. Pharmacological blockade of HDACs using Trichostatin A (TSA) increased histone acetylation levels in the amputated tail. Furthermore, treatment with TSA or another HDAC inhibitor, valproic acid, specifically inhibited regeneration. Over-expression of wild-type Mad3, a transcriptional repressor known to associate in a complex with HDACs via Sin3, inhibited regeneration. Similarly, expression of a Mad3 mutant lackin