Latrunculin A Treatment Prevents Abnormal Chromosome Segregation for Successful Development of Cloned Embryos

Yukari Terashita, Kazuo Yamagata, Mikiko Tokoro, Fumiaki Itoi, Sayaka Wakayama, Chong Li, Eimei Sato, Kentaro Tanemura, Teruhiko Wakayama

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Somatic cell nuclear transfer to an enucleated oocyte is used for reprogramming somatic cells with the aim of achieving totipotency, but most cloned embryos die in the uterus after transfer. While modifying epigenetic states of cloned embryos can improve their development, the production rate of cloned embryos can also be enhanced by changing other factors. It has already been shown that abnormal chromosome segregation (ACS) is a major cause of the developmental failure of cloned embryos and that Latrunculin A (LatA), an actin polymerization inhibitor, improves F-actin formation and birth rate of cloned embryos. Since F-actin is important for chromosome congression in embryos, here we examined the relation between ACS and F-actin in cloned embryos. Using LatA treatment, the occurrence of ACS decreased significantly whereas cloned embryo-specific epigenetic abnormalities such as dimethylation of histone H3 at lysine 9 (H3K9me2) could not be corrected. In contrast, when H3K9me2 was normalized using the G9a histone methyltransferase inhibitor BIX-01294, the Magea2 gene-essential for normal development but never before expressed in cloned embryos-was expressed. However, this did not increase the cloning success rate. Thus, non-epigenetic factors also play an important role in determining the efficiency of mouse cloning.

Original languageEnglish
Article numbere78380
JournalPloS one
Volume8
Issue number10
DOIs
Publication statusPublished - 2013 Oct 24

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Terashita, Y., Yamagata, K., Tokoro, M., Itoi, F., Wakayama, S., Li, C., Sato, E., Tanemura, K., & Wakayama, T. (2013). Latrunculin A Treatment Prevents Abnormal Chromosome Segregation for Successful Development of Cloned Embryos. PloS one, 8(10), [e78380]. https://doi.org/10.1371/journal.pone.0078380